Protein Kinases Signaling in Pancreatic Beta-cells Death and Type 2 Diabetes.
ER (endoplasmic reticulum) stress
Fas receptors (FasR)
Glucose-stimulated insulin secretion (GSIS)
Human islet amyloid polypeptide (hIAPP)
Reactive oxygen species (ROS)
Reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase
Saturated free fatty acids (SFFA)
Type 2 diabetes (T2D)
β-Cell death
β-Cell dysfunction
Journal
Advances in experimental medicine and biology
ISSN: 0065-2598
Titre abrégé: Adv Exp Med Biol
Pays: United States
ID NLM: 0121103
Informations de publication
Date de publication:
2021
2021
Historique:
entrez:
4
2
2021
pubmed:
5
2
2021
medline:
16
2
2021
Statut:
ppublish
Résumé
Type 2 diabetes (T2D) is a worldwide serious public health problem. Insulin resistance and β-cell failure are the two major components of T2D pathology. In addition to defective endoplasmic reticulum (ER) stress signaling due to glucolipotoxicity, β-cell dysfunction or β-cell death initiates the deleterious vicious cycle observed in T2D. Although the primary cause is still unknown, overnutrition that contributes to the induction of the state of low-grade inflammation, and the activation of various protein kinases-related metabolic pathways are main factors leading to T2D. In this chapter following subjects, which have critical checkpoints regarding β-cell fate and protein kinases pathways are discussed; hyperglycemia-induced β-cell failure, chronic accumulation of unfolded protein in β-cells, the effect of intracellular reactive oxygen species (ROS) signaling to insulin secretion, excessive saturated free fatty acid-induced β-cell apoptosis, mitophagy dysfunction, proinflammatory responses and insulin resistance, and the reprogramming of β-cell for differentiation or dedifferentiation in T2D. There is much debate about selecting proposed therapeutic strategies to maintain or enhance optimal β-cell viability for adequate insulin secretion in T2D. However, in order to achieve an effective solution in the treatment of T2D, more intensive clinical trials are required on newer therapeutic options based on protein kinases signaling pathways.
Identifiants
pubmed: 33539017
doi: 10.1007/978-3-030-49844-3_8
doi:
Substances chimiques
Insulin
0
Protein Kinases
EC 2.7.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
195-227Références
Ahn M, Yoder SM, Wang Z, Oh E, Ramalingam L, Tunduguru R, Thurmond DC. The p21-activated kinase (PAK1) is involved in diet-induced beta cell mass expansion and survival in mice and human islets. Diabetologia. 2016;59:2145–55. https://doi.org/10.1007/s00125-016-4042-0 .
doi: 10.1007/s00125-016-4042-0
pubmed: 27394663
pmcid: 5266538
Akash MSH, Rehman K, Liaqat A. Tumor necrosis factor-alpha: role in development of insulin resistance and pathogenesis of type 2 diabetes mellitus. J Cell Biochem. 2018;119:105–10. https://doi.org/10.1002/jcb.26174 .
doi: 10.1002/jcb.26174
pubmed: 28569437
Appenzeller-Herzog C, Hall MN. Bidirectional crosstalk between endoplasmic reticulum stress and mTOR signaling. Trends Cell Biol. 2012;22:274–82. https://doi.org/10.1016/j.tcb.2012.02.006 .
doi: 10.1016/j.tcb.2012.02.006
pubmed: 22444729
Artner I, Le Lay J, Hang Y, Elghazi L, Schisler JC, Henderson E, Sosa-Pineda B, Stein R. MafB: an activator of the glucagon gene expressed in developing islet alpha- and β-cells. Diabetes. 2006;55:297–304. https://doi.org/10.2337/diabetes.55.02.06.db05-0946 .
Bachar E, Ariav Y, Ketzinel-Gilad M, Cerasi E, Kaiser N, Leibowitz G. Glucose amplifies fatty acid-induced endoplasmic reticulum stress in pancreatic β-cells via activation of mTORC1. PLoS One. 2009;4:e4954. https://doi.org/10.1371/journal.pone.0004954 .
Bachar-Wikstrom E, Wikstrom JD, Kaiser N, Cerasi E, Leibowitz G. Improvement of ER stress-induced diabetes by stimulating autophagy. Autophagy. 2013;9:626–8. https://doi.org/10.4161/auto.23642 .
doi: 10.4161/auto.23642
pubmed: 23380813
pmcid: 3627683
Back SH, Scheuner D, Han J, Song B, Ribick M, Wang J, Gildersleeve RD, Pennathur S, Kaufman RJ. Translation attenuation through eIF2alpha phosphorylation prevents oxidative stress and maintains the differentiated state in beta cells. Cell Metab. 2009;10:13–26. https://doi.org/10.1016/j.cmet.2009.06.002 .
doi: 10.1016/j.cmet.2009.06.002
pubmed: 19583950
pmcid: 2742645
Bagnati M, Ogunkolade BW, Marshall C, Tucci C, Hanna K, Jones TA, Bugliani M, Nedjai B, Caton PW, Kieswich J, Yaqoob MM, Ball GR, Marchetti P, Hitman GA, Turner MD. Glucolipotoxicity initiates pancreatic β-cell death through TNFR5/CD40-mediated STAT1 and NF-κB activation. Cell Death Dis. 2016;7:e2329. https://doi.org/10.1038/cddis.2016.203 .
doi: 10.1038/cddis.2016.203
pubmed: 27512950
pmcid: 5108311
Balcazar N, Sathyamurthy A, Elghazi L, Gould A, Weiss A, Shiojima I, Walsh K, Bernal-Mizrachi E. mTORC1 activation regulates beta-cell mass and proliferation by modulation of cyclin D2 synthesis and stability. J Biol Chem. 2009;284:7832–42. https://doi.org/10.1074/jbc.M807458200 .
doi: 10.1074/jbc.M807458200
pubmed: 19144649
pmcid: 2658077
Banaei-Bouchareb L, Peuchmaur M, Czernichow P, Polak M. A transient microenvironment loaded mainly with macrophages in the early developing human pancreas. J Endocrinol. 2006;188:467–80. https://doi.org/10.1677/joe.1.06225 .
doi: 10.1677/joe.1.06225
pubmed: 16522727
Barbu A, Welsh N, Saldeen J. Cytokine-induced apoptosis and necrosis are preceded by disruption of the mitochondrial membrane potential (Deltapsi(m)) in pancreatic RINm5F cells: prevention by Bcl-2. Mol Cell Endocrinol. 2002;190:75–82. https://doi.org/10.1016/s0303-7207(02)00009-6 .
doi: 10.1016/s0303-7207(02)00009-6
pubmed: 11997180
Bensellam M, Jonas J-C, Laybutt DR. Mechanisms of β-cell dedifferentiation in diabetes: recent findings and future research directions. J Endocrinol. 2018;236:R109–43. https://doi.org/10.1530/JOE-17-0516 .
doi: 10.1530/JOE-17-0516
pubmed: 29203573
Biden TJ, Boslem E, Chu KY, Sue N. Lipotoxic endoplasmic reticulum stress, β-cell failure, and type 2 diabetes mellitus. Trends Endocrinol Metab. 2014;25:389–98. https://doi.org/10.1016/j.tem.2014.02.003 .
Blandino-Rosano M, Chen AY, Scheys JO, Alejandro EU, Gould AP, Taranukha T, Elghazi L, Cras-Méneur C, Bernal-Mizrachi E. mTORC1 signaling and regulation of pancreatic β-cell mass. Cell Cycle. 2012;11:1892–902. https://doi.org/10.4161/cc.20036 .
doi: 10.4161/cc.20036
pubmed: 22544327
pmcid: 3359119
Boerner BP, George NM, Mir SUR, Sarvetnick NE. WS6 induces both alpha and beta cell proliferation without affecting differentiation or viability. Endocr J. 2015;62:379–86. https://doi.org/10.1507/endocrj.EJ14-0449 .
doi: 10.1507/endocrj.EJ14-0449
pubmed: 25739404
pmcid: 4876955
Bouzakri K, Ribaux P, Halban PA. Silencing mitogen-activated protein 4 kinase 4 (MAP4K4) protects beta cells from tumor necrosis factor-alpha-induced decrease of IRS-2 and inhibition of glucose-stimulated insulin secretion. J Biol Chem. 2009;284:27892–8. https://doi.org/10.1074/jbc.M109.048058 .
doi: 10.1074/jbc.M109.048058
pubmed: 19690174
pmcid: 2788840
Bramanti V, Grasso S, Tibullo D, Giallongo C, Raciti G, Viola M, Avola R. Modulation of extracellular signal-related kinase, cyclin D1, glial fibrillary acidic protein, and vimentin expression in estradiol-pretreated astrocyte cultures treated with competence and progression growth factors. J Neurosci Res. 2015;93:1378–87. https://doi.org/10.1002/jnr.23606 .
doi: 10.1002/jnr.23606
pubmed: 26053243
Bratanova-Tochkova TK, Cheng H, Daniel S, Gunawardana S, Liu Y-J, Mulvaney-Musa J, Schermerhorn T, Straub SG, Yajima H, Sharp GWG. Triggering and augmentation mechanisms, granule pools, and biphasic insulin secretion. Diabetes. 2002;51(Suppl 1):S83–90. https://doi.org/10.2337/diabetes.51.2007.s83 .
doi: 10.2337/diabetes.51.2007.s83
pubmed: 11815463
Brozzi F, Gerlo S, Grieco FA, Juusola M, Balhuizen A, Lievens S, Gysemans C, Bugliani M, Mathieu C, Marchetti P, Tavernier J, Eizirik DL. Ubiquitin D regulates IRE1α/c-Jun N-terminal kinase (JNK) protein-dependent apoptosis in pancreatic Beta cells. J Biol Chem. 2016;291:12040–56. https://doi.org/10.1074/jbc.M115.704619 .
doi: 10.1074/jbc.M115.704619
pubmed: 27044747
pmcid: 4933257
Buteau J, Accili D. Regulation of pancreatic beta-cell function by the forkhead protein FoxO1. Diabetes Obes Metab. 2007;9(Suppl 2):140–6. https://doi.org/10.1111/j.1463-1326.2007.00782.x .
doi: 10.1111/j.1463-1326.2007.00782.x
pubmed: 17919188
Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes. 2003;52:102–10. https://doi.org/10.2337/diabetes.52.1.102 .
doi: 10.2337/diabetes.52.1.102
pubmed: 12502499
Butler PC, Meier JJ, Butler AE, Bhushan A. The replication of beta cells in normal physiology, in disease and for therapy. Nat Clin Pract Endocrinol Metab. 2007;3:758–68. https://doi.org/10.1038/ncpendmet0647 .
doi: 10.1038/ncpendmet0647
pubmed: 17955017
Caillon L, Hoffmann ARF, Botz A, Khemtemourian L. Molecular structure, membrane interactions, and toxicity of the islet amyloid polypeptide in type 2 diabetes mellitus. J Diabetes Res. 2016;2016:5639875. https://doi.org/10.1155/2016/5639875 .
doi: 10.1155/2016/5639875
pubmed: 26636105
Chan JY, Luzuriaga J, Maxwell EL, West PK, Bensellam M, Laybutt DR. The balance between adaptive and apoptotic unfolded protein responses regulates β-cell death under ER stress conditions through XBP1, CHOP and JNK. Mol Cell Endocrinol. 2015;413:189–201. https://doi.org/10.1016/j.mce.2015.06.025 .
doi: 10.1016/j.mce.2015.06.025
pubmed: 26135354
Chen Y, Qiao F, Zhao Y, Wang Y, Liu G. HMGB1 is activated in type 2 diabetes mellitus patients and in mesangial cells in response to high glucose. Int J Clin Exp Pathol. 2015;8:6683–91.
pubmed: 26261550
pmcid: 4525884
Chen L, Liu C, Gao J, Xie Z, Chan LWC, Keating DJ, Yang Y, Sun J, Zhou F, Wei Y, Men X, Yang S. Inhibition of Miro1 disturbs mitophagy and pancreatic β-cell function interfering insulin release via IRS-Akt-Foxo1 in diabetes. Oncotarget. 2017;8:90693–705. https://doi.org/10.18632/oncotarget.20963 .
doi: 10.18632/oncotarget.20963
pubmed: 29207597
pmcid: 5710878
Chera S, Baronnier D, Ghila L, Cigliola V, Jensen JN, Gu G, Furuyama K, Thorel F, Gribble FM, Reimann F, Herrera PL. Diabetes recovery by age-dependent conversion of pancreatic δ-cells into insulin producers. Nature. 2014;514:503–7. https://doi.org/10.1038/nature13633 .
doi: 10.1038/nature13633
pubmed: 25141178
pmcid: 4209186
Cinti F, Bouchi R, Kim-Muller JY, Ohmura Y, Sandoval PR, Masini M, Marselli L, Suleiman M, Ratner LE, Marchetti P, Accili D. Evidence of β-cell dedifferentiation in human type 2 diabetes. J Clin Endocrinol Metab. 2016;101:1044–54. https://doi.org/10.1210/jc.2015-2860 .
doi: 10.1210/jc.2015-2860
pubmed: 26713822
Cnop M, Ladriere L, Hekerman P, Ortis F, Cardozo AK, Dogusan Z, Flamez D, Boyce M, Yuan J, Eizirik DL. Selective inhibition of eukaryotic translation initiation factor 2 alpha dephosphorylation potentiates fatty acid-induced endoplasmic reticulum stress and causes pancreatic beta-cell dysfunction and apoptosis. J Biol Chem. 2007;282:3989–97. https://doi.org/10.1074/jbc.M607627200 .
doi: 10.1074/jbc.M607627200
pubmed: 17158450
Collombat P, Mansouri A, Hecksher-Sorensen J, Serup P, Krull J, Gradwohl G, Gruss P. Opposing actions of Arx and Pax4 in endocrine pancreas development. Genes Dev. 2003;17:2591–603. https://doi.org/10.1101/gad.269003 .
doi: 10.1101/gad.269003
pubmed: 14561778
pmcid: 218152
Collombat P, Hecksher-Sørensen J, Broccoli V, Krull J, Ponte I, Mundiger T, Smith J, Gruss P, Serup P, Mansouri A. The simultaneous loss of Arx and Pax4 genes promotes a somatostatin-producing cell fate specification at the expense of the alpha- and beta-cell lineages in the mouse endocrine pancreas. Development. 2005;132:2969–80. https://doi.org/10.1242/dev.01870 .
doi: 10.1242/dev.01870
pubmed: 15930104
Collombat P, Hecksher-Sørensen J, Krull J, Berger J, Riedel D, Herrera PL, Serup P, Mansouri A. Embryonic endocrine pancreas and mature beta cells acquire alpha and PP cell phenotypes upon Arx misexpression. J Clin Invest. 2007;117:961–70. https://doi.org/10.1172/JCI29115 .
doi: 10.1172/JCI29115
pubmed: 17404619
pmcid: 1839241
Collombat P, Xu X, Ravassard P, Sosa-Pineda B, Dussaud S, Billestrup N, Madsen OD, Serup P, Heimberg H, Mansouri A. The ectopic expression of Pax4 in the mouse pancreas converts progenitor cells into alpha and subsequently beta cells. Cell. 2009;138:449–62. https://doi.org/10.1016/j.cell.2009.05.035 .
doi: 10.1016/j.cell.2009.05.035
pubmed: 19665969
pmcid: 2792203
Costes S, Langen R, Gurlo T, Matveyenko AV, Butler PC. β-cell failure in type 2 diabetes: a case of asking too much of too few? Diabetes. 2013;62:327–35. https://doi.org/10.2337/db12-1326 .
doi: 10.2337/db12-1326
pubmed: 23349537
pmcid: 3554362
Courtney M, Gjernes E, Druelle N, Ravaud C, Vieira A, Ben-Othman N, Pfeifer A, Avolio F, Leuckx G, Lacas-Gervais S, Burel-Vandenbos F, Ambrosetti D, Hecksher-Sorensen J, Ravassard P, Heimberg H, Mansouri A, Collombat P. The inactivation of Arx in pancreatic α-cells triggers their neogenesis and conversion into functional β-like cells. PLoS Genet. 2013;9:e1003934. https://doi.org/10.1371/journal.pgen.1003934 .
doi: 10.1371/journal.pgen.1003934
pubmed: 24204325
pmcid: 3814322
Cross DA, Alessi DR, Cohen P, Andjelkovich M, Hemmings BA. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature. 1995;378:785–9. https://doi.org/10.1038/378785a0 .
doi: 10.1038/378785a0
pubmed: 8524413
Cullinan SB, Diehl JA. PERK-dependent activation of Nrf2 contributes to redox homeostasis and cell survival following endoplasmic reticulum stress. J Biol Chem. 2004;279:20108–17. https://doi.org/10.1074/jbc.M314219200 .
doi: 10.1074/jbc.M314219200
pubmed: 14978030
Dhawan S, Georgia S, Tschen S-I, Fan G, Bhushan A. Pancreatic β-cell identity is maintained by DNA methylation-mediated repression of Arx. Dev Cell. 2011;20:419–29. https://doi.org/10.1016/j.devcel.2011.03.012 .
Dirice E, Walpita D, Vetere A, Meier BC, Kahraman S, Hu J, Dančík V, Burns SM, Gilbert TJ, Olson DE, Clemons PA, Kulkarni RN, Wagner BK. Inhibition of DYRK1A stimulates human β-cell proliferation. Diabetes. 2016;65:1660–71. https://doi.org/10.2337/db15-1127 .
doi: 10.2337/db15-1127
pubmed: 26953159
pmcid: 4878416
Druelle N, Vieira A, Shabro A, Courtney M, Mondin M, Rekima S, Napolitano T, Silvano S, Navarro-Sanz S, Hadzic B, Avolio F, Rassoulzadegan M, Schmid HA, Mansouri A, Collombat P. Ectopic expression of Pax4 in pancreatic δ cells results in β-like cell neogenesis. J Cell Biol. 2017;216:4299–311. https://doi.org/10.1083/jcb.201704044 .
doi: 10.1083/jcb.201704044
pubmed: 29025873
pmcid: 5716283
Eguchi K, Nagai R. Islet inflammation in type 2 diabetes and physiology. J Clin Invest. 2017;127:14–23. https://doi.org/10.1172/JCI88877 .
doi: 10.1172/JCI88877
pubmed: 28045399
pmcid: 5199688
Eguchi K, Manabe I, Oishi-Tanaka Y, Ohsugi M, Kono N, Ogata F, Yagi N, Ohto U, Kimoto M, Miyake K, Tobe K, Arai H, Kadowaki T, Nagai R. Saturated fatty acid and TLR signaling link β-cell dysfunction and islet inflammation. Cell Metab. 2012;15:518–33. https://doi.org/10.1016/j.cmet.2012.01.023 .
Eitel K, Staiger H, Rieger J, Mischak H, Brandhorst H, Brendel MD, Bretzel RG, Häring H-U, Kellerer M. Protein kinase C delta activation and translocation to the nucleus are required for fatty acid-induced apoptosis of insulin-secreting cells. Diabetes. 2003;52:991–7. https://doi.org/10.2337/diabetes.52.4.991 .
doi: 10.2337/diabetes.52.4.991
pubmed: 12663471
Eizirik DL, Miani M, Cardozo AK. Signalling danger: endoplasmic reticulum stress and the unfolded protein response in pancreatic islet inflammation. Diabetologia. 2013;56:234–41. https://doi.org/10.1007/s00125-012-2762-3 .
doi: 10.1007/s00125-012-2762-3
pubmed: 23132339
Engel MFM, Yigittop H, Elgersma RC, Rijkers DTS, Liskamp RMJ, de Kruijff B, Höppener JWM, Antoinette Killian J. Islet amyloid polypeptide inserts into phospholipid monolayers as monomer. J Mol Biol. 2006;356:783–9. https://doi.org/10.1016/j.jmb.2005.12.020 .
doi: 10.1016/j.jmb.2005.12.020
pubmed: 16403520
Engel MFM, Khemtémourian L, Kleijer CC, Meeldijk HJD, Jacobs J, Verkleij AJ, de Kruijff B, Killian JA, Höppener JWM. Membrane damage by human islet amyloid polypeptide through fibril growth at the membrane. Proc Natl Acad Sci U S A. 2008;105:6033–8. https://doi.org/10.1073/pnas.0708354105 .
doi: 10.1073/pnas.0708354105
pubmed: 18408164
pmcid: 2329711
Fang D, Huang Z, Guan H, Liu J, Yao B, Xiao H, Li Y. The Akt/FoxO1/p27 pathway mediates the proliferative action of liraglutide in β-cells. Mol Med Rep. 2012;5:233–8. https://doi.org/10.3892/mmr.2011.607 .
Fang N, Zhang W, Xu S, Lin H, Wang Z, Liu H, Fang Q, Li C, Peng L, Lou J. TRIB3 alters endoplasmic reticulum stress-induced β-cell apoptosis via the NF-κB pathway. Metab Clin Exp. 2014;63:822–30. https://doi.org/10.1016/j.metabol.2014.03.003 .
doi: 10.1016/j.metabol.2014.03.003
pubmed: 24746137
Fatrai S, Elghazi L, Balcazar N, Cras-Méneur C, Krits I, Kiyokawa H, Bernal-Mizrachi E. Akt induces beta-cell proliferation by regulating cyclin D1, cyclin D2, and p21 levels and cyclin-dependent kinase-4 activity. Diabetes. 2006;55:318–25. https://doi.org/10.2337/diabetes.55.02.06.db05-0757 .
doi: 10.2337/diabetes.55.02.06.db05-0757
pubmed: 16443763
Feng Z, Zhang H, Levine AJ, Jin S. The coordinate regulation of the p53 and mTOR pathways in cells. Proc Natl Acad Sci U S A. 2005;102:8204–9. https://doi.org/10.1073/pnas.0502857102 .
doi: 10.1073/pnas.0502857102
pubmed: 15928081
pmcid: 1142118
Fernández-Millán E, Martín MA, Goya L, Lizárraga-Mollinedo E, Escrivá F, Ramos S, Álvarez C. Glucagon-like peptide-1 improves beta-cell antioxidant capacity via extracellular regulated kinases pathway and Nrf2 translocation. Free Radic Biol Med. 2016;95:16–26. https://doi.org/10.1016/j.freeradbiomed.2016.03.002 .
doi: 10.1016/j.freeradbiomed.2016.03.002
pubmed: 26968794
Ferrannini E. The stunned beta cell: a brief history. Cell Metab. 2010;11:349–52. https://doi.org/10.1016/j.cmet.2010.04.009 .
doi: 10.1016/j.cmet.2010.04.009
pubmed: 20444416
Fonseca SG, Burcin M, Gromada J, Urano F. Endoplasmic reticulum stress in β-cells and development of diabetes. Curr Opin Pharmacol. 2009;9:763–70. https://doi.org/10.1016/j.coph.2009.07.003 .
Fonseca SG, Gromada J, Urano F. Endoplasmic reticulum stress and pancreatic β-cell death. Trends Endocrinol Metab. 2011;22:266–74. https://doi.org/10.1016/j.tem.2011.02.008 .
doi: 10.1016/j.tem.2011.02.008
pubmed: 21458293
pmcid: 3130122
Fontés G, Semache M, Hagman DK, Tremblay C, Shah R, Rhodes CJ, Rutter J, Poitout V. Involvement of per-Arnt-Sim kinase and extracellular-regulated kinases-1/2 in palmitate inhibition of insulin gene expression in pancreatic β-cells. Diabetes. 2009;58:2048–58. https://doi.org/10.2337/db08-0579 .
Fridlyand LE, Philipson LH. Does the glucose-dependent insulin secretion mechanism itself cause oxidative stress in pancreatic β-cells? Diabetes. 2004;53:1942–8. https://doi.org/10.2337/diabetes.53.8.1942 .
Fu A, Ng AC-H, Depatie C, Wijesekara N, He Y, Wang G-S, Bardeesy N, Scott FW, Touyz RM, Wheeler MB, Screaton RA. Loss of Lkb1 in adult beta cells increases beta cell mass and enhances glucose tolerance in mice. Cell Metab. 2009;10:285–95. https://doi.org/10.1016/j.cmet.2009.08.008 .
doi: 10.1016/j.cmet.2009.08.008
pubmed: 19808021
Fu Z, Gilbert ER, Liu D. Regulation of insulin synthesis and secretion and pancreatic Beta-cell dysfunction in diabetes. Curr Diabetes Rev. 2013;9:25–53.
pubmed: 22974359
pmcid: 3934755
Fürstova V, Kopska T, James RFL, Kovar J. Comparison of the effect of individual saturated and unsaturated fatty acids on cell growth and death induction in the human pancreatic beta-cell line NES2Y. Life Sci. 2008;82:684–91. https://doi.org/10.1016/j.lfs.2007.12.023 .
doi: 10.1016/j.lfs.2007.12.023
pubmed: 18272185
Gao T, McKenna B, Li C, Reichert M, Nguyen J, Singh T, Yang C, Pannikar A, Doliba N, Zhang T, Stoffers DA, Edlund H, Matschinsky F, Stein R, Stanger BZ. Pdx1 maintains β-cell identity and function by repressing an α cell program. Cell Metab. 2014;19:259–71. https://doi.org/10.1016/j.cmet.2013.12.002 .
Gao L, Tang W, Ding Z, Wang D, Qi X, Wu H, Guo J. Protein-binding function of RNA-dependent protein kinase promotes proliferation through TRAF2/RIP1/NF-κB/c-Myc pathway in pancreatic β-cells. Mol Med. 2015;21:154–66. https://doi.org/10.2119/molmed.2014.00235 .
Gerst F, Kaiser G, Panse M, Sartorius T, Pujol A, Hennige AM, Machicao F, Lammers R, Bosch F, Häring H-U, Ullrich S. Protein kinase Cδ regulates nuclear export of FOXO1 through phosphorylation of the chaperone 14-3-3ζ. Diabetologia. 2015;58:2819–31. https://doi.org/10.1007/s00125-015-3744-z .
doi: 10.1007/s00125-015-3744-z
pubmed: 26363783
Gjoni E, Brioschi L, Cinque A, Coant N, Islam MN, Ng CK-Y, Verderio C, Magnan C, Riboni L, Viani P, Le Stunff H, Giussani P. Glucolipotoxicity impairs ceramide flow from the endoplasmic reticulum to the Golgi apparatus in INS-1 β-cells. PLoS One. 2014;9:e110875. https://doi.org/10.1371/journal.pone.0110875 .
doi: 10.1371/journal.pone.0110875
pubmed: 25350564
pmcid: 4211692
Granata R, Settanni F, Biancone L, Trovato L, Nano R, Bertuzzi F, Destefanis S, Annunziata M, Martinetti M, Catapano F, Ghè C, Isgaard J, Papotti M, Ghigo E, Muccioli G. Acylated and unacylated ghrelin promote proliferation and inhibit apoptosis of pancreatic β-cells and human islets: involvement of 3′,5′-cyclic adenosine monophosphate/protein kinase a, extracellular signal-regulated kinase 1/2, and phosphatidyl inositol 3-kinase/Akt signaling. Endocrinology. 2007;148:512–29. https://doi.org/10.1210/en.2006-0266 .
Granot Z, Swisa A, Magenheim J, Stolovich-Rain M, Fujimoto W, Manduchi E, Miki T, Lennerz JK, Stoeckert CJ, Meyuhas O, Seino S, Permutt MA, Piwnica-Worms H, Bardeesy N, Dor Y. LKB1 regulates pancreatic beta cell size, polarity, and function. Cell Metab. 2009;10:296–308. https://doi.org/10.1016/j.cmet.2009.08.010 .
doi: 10.1016/j.cmet.2009.08.010
pubmed: 19808022
pmcid: 2790403
Grewal AS, Sekhon BS, Lather V. Recent updates on glucokinase activators for the treatment of type 2 diabetes mellitus. Mini Rev Med Chem. 2014;14:585–602. https://doi.org/10.2174/1389557514666140722082713 .
doi: 10.2174/1389557514666140722082713
pubmed: 25052034
Gross DN, van den Heuvel APJ, Birnbaum MJ. The role of FoxO in the regulation of metabolism. Oncogene. 2008;27:2320–36. https://doi.org/10.1038/onc.2008.25 .
doi: 10.1038/onc.2008.25
pubmed: 18391974
Guan B-J, Krokowski D, Majumder M, Schmotzer CL, Kimball SR, Merrick WC, Koromilas AE, Hatzoglou M. Translational control during endoplasmic reticulum stress beyond phosphorylation of the translation initiation factor eIF2α. J Biol Chem. 2014;289:12593–611. https://doi.org/10.1074/jbc.M113.543215 .
doi: 10.1074/jbc.M113.543215
pubmed: 24648524
pmcid: 4007450
Guo J, Qian Y, Xi X, Hu X, Zhu J, Han X. Blockage of ceramide metabolism exacerbates palmitate inhibition of pro-insulin gene expression in pancreatic β-cells. Mol Cell Biochem. 2010;338:283–90. https://doi.org/10.1007/s11010-009-0362-4 .
Guo S, Dai C, Guo M, Taylor B, Harmon JS, Sander M, Robertson RP, Powers AC, Stein R. Inactivation of specific β-cell transcription factors in type 2 diabetes. J Clin Invest. 2013;123:3305–16. https://doi.org/10.1172/JCI65390 .
Guo VY, Cao B, Cai C, Cheng KK-Y, Cheung BMY. Fetuin-a levels and risk of type 2 diabetes mellitus: a systematic review and meta-analysis. Acta Diabetol. 2018;55:87–98. https://doi.org/10.1007/s00592-017-1068-9
pubmed: 29127490
Gwiazda KS, Yang T-LB, Lin Y, Johnson JD. Effects of palmitate on ER and cytosolic Ca2+ homeostasis in β-cells. Am J Physiol Endocrinol Metab. 2009;296:E690–701. https://doi.org/10.1152/ajpendo.90525.2008
Han D, Yang B, Olson LK, Greenstein A, Baek S-H, Claycombe KJ, Goudreau JL, Yu S-W, Kim E-K. Activation of autophagy through modulation of 5’-AMP-activated protein kinase protects pancreatic β-cells from high glucose. Biochem J. 2010;425:541–51. https://doi.org/10.1042/BJ20090429
Hanada K, Kumagai K, Tomishige N, Yamaji T. CERT-mediated trafficking of ceramide. Biochim Biophys Acta. 2009;1791:684–91. https://doi.org/10.1016/j.bbalip.2009.01.006
pubmed: 19416656
Harding HP, Zhang Y, Ron D. Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase. Nature. 1999;397:271–4. https://doi.org/10.1038/16729
pubmed: 9930704
Hennige AM, Ranta F, Heinzelmann I, Düfer M, Michael D, Braumüller H, Lutz SZ, Lammers R, Drews G, Bosch F, Häring H-U, Ullrich S. Overexpression of kinase-negative protein kinase Cdelta in pancreatic β-cells protects mice from diet-induced glucose intolerance and beta-cell dysfunction. Diabetes. 2010;59:119–27. https://doi.org/10.2337/db09-0512
Herrera PL. Adult insulin- and glucagon-producing cells differentiate from two independent cell lineages. Development. 2000;127:2317–22.
pubmed: 10804174
Herrera PL, Huarte J, Zufferey R, Nichols A, Mermillod B, Philippe J, Muniesa P, Sanvito F, Orci L, Vassalli JD. Ablation of islet endocrine cells by targeted expression of hormone-promoter-driven toxigenes. Proc Natl Acad Sci U S A. 1994;91:12999–3003. https://doi.org/10.1073/pnas.91.26.12999
pubmed: 7809163
pmcid: 45568
Hetz C, Martinon F, Rodriguez D, Glimcher LH. The unfolded protein response: integrating stress signals through the stress sensor IRE1α. Physiol Rev. 2011;91:1219–43. https://doi.org/10.1152/physrev.00001.2011
pubmed: 22013210
Horn S, Hughes MA, Schilling R, Sticht C, Tenev T, Ploesser M, Meier P, Sprick MR, MacFarlane M, Leverkus M. Caspase-10 negatively regulates Caspase-8-mediated cell death, switching the response to CD95L in favor of NF-κB activation and cell survival. Cell Rep. 2017;19:785–97. https://doi.org/10.1016/j.celrep.2017.04.010
pubmed: 28445729
pmcid: 5413585
Hou N, Torii S, Saito N, Hosaka M, Takeuchi T. Reactive oxygen species-mediated pancreatic beta-cell death is regulated by interactions between stress-activated protein kinases, p38 and c-Jun N-terminal kinase, and mitogen-activated protein kinase phosphatases. Endocrinology. 2008;149:1654–65. https://doi.org/10.1210/en.2007-0988
pubmed: 18187551
Huang S, Zhu M, Wu W, Rashid A, Liang Y, Hou L, Ning Q, Luo X. Valproate pretreatment protects pancreatic β-cells from palmitate-induced ER stress and apoptosis by inhibiting glycogen synthase kinase-3β. J Biomed Sci. 2014;21:38. https://doi.org/10.1186/1423-0127-21-38
pubmed: 24884462
pmcid: 4084580
Hui Q, Asadi A, Park YJ, Kieffer TJ, Ao Z, Warnock GL, Marzban L. Amyloid formation disrupts the balance between interleukin-1β and interleukin-1 receptor antagonist in human islets. Mol Metab. 2017;6:833–44. https://doi.org/10.1016/j.molmet.2017.05.016
pubmed: 28752047
pmcid: 5518725
Hull RL, Westermark GT, Westermark P, Kahn SE. Islet amyloid: a critical entity in the pathogenesis of type 2 diabetes. J Clin Endocrinol Metab. 2004;89:3629–43. https://doi.org/10.1210/jc.2004-0405
pubmed: 15292279
Humphrey RK, Newcomb CJ, Yu S-MA, Hao E, Yu D, Krajewski S, Du K, Jhala US. Mixed lineage kinase-3 stabilizes and functionally cooperates with TRIBBLES-3 to compromise mitochondrial integrity in cytokine-induced death of pancreatic beta cells. J Biol Chem. 2010;285:22426–36. https://doi.org/10.1074/jbc.M110.123786
pubmed: 20421299
pmcid: 2903363
Humphrey RK, Ray A, Gonuguntla S, Hao E, Jhala US. Loss of TRB3 alters dynamics of MLK3-JNK signaling and inhibits cytokine-activated pancreatic beta cell death. J Biol Chem. 2014;289:29994–30004. https://doi.org/10.1074/jbc.M114.575613
pubmed: 25204656
pmcid: 4208007
Inoki K, Ouyang H, Zhu T, Lindvall C, Wang Y, Zhang X, Yang Q, Bennett C, Harada Y, Stankunas K, Wang C-Y, He X, MacDougald OA, You M, Williams BO, Guan K-L. TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth. Cell. 2006;126:955–68. https://doi.org/10.1016/j.cell.2006.06.055
pubmed: 16959574
Irmler M, Thome M, Hahne M, Schneider P, Hofmann K, Steiner V, Bodmer JL, Schröter M, Burns K, Mattmann C, Rimoldi D, French LE, Tschopp J. Inhibition of death receptor signals by cellular FLIP. Nature. 1997;388:190–5. https://doi.org/10.1038/40657
pubmed: 9217161
Ishizuka N, Yagui K, Tokuyama Y, Yamada K, Suzuki Y, Miyazaki J, Hashimoto N, Makino H, Saito Y, Kanatsuka A. Tumor necrosis factor alpha signaling pathway and apoptosis in pancreatic beta cells. Metab Clin Exp. 1999;48:1485–92. https://doi.org/10.1016/s0026-0495(99)90234-2
pubmed: 10599977
Itoh N, Okamoto H. Translational control of proinsulin synthesis by glucose. Nature. 1980;283:100–2. https://doi.org/10.1038/283100a0
pubmed: 6985712
Jaikaran ETAS, Nilsson MR, Clark A. Pancreatic beta-cell granule peptides form heteromolecular complexes which inhibit islet amyloid polypeptide fibril formation. Biochem J. 2004;377:709–16. https://doi.org/10.1042/BJ20030852
pubmed: 14565847
pmcid: 1223903
Jansson L, Eizirik DL, Pipeleers DG, Borg LA, Hellerström C, Andersson A. Impairment of glucose-induced insulin secretion in human pancreatic islets transplanted to diabetic nude mice. J Clin Invest. 1995;96:721–6. https://doi.org/10.1172/JCI118115
pubmed: 7635965
pmcid: 185255
Jansson D, Ng AC-H, Fu A, Depatie C, Al Azzabi M, Screaton RA. Glucose controls CREB activity in islet cells via regulated phosphorylation of TORC2. Proc Natl Acad Sci U S A. 2008;105:10161–6. https://doi.org/10.1073/pnas.0800796105
pubmed: 18626018
pmcid: 2481316
Jensen MV, Joseph JW, Ronnebaum SM, Burgess SC, Sherry AD, Newgard CB. Metabolic cycling in control of glucose-stimulated insulin secretion. Am J Physiol Endocrinol Metab. 2008;295:E1287–97. https://doi.org/10.1152/ajpendo.90604.2008
pubmed: 18728221
pmcid: 2603555
Jung TW, Lee MW, Lee YJ, Kim SM. Metformin prevents endoplasmic reticulum stress-induced apoptosis through AMPK-PI3K-c-Jun NH2 pathway. Biochem Biophys Res Commun. 2012;417:147–52. https://doi.org/10.1016/j.bbrc.2011.11.073
pubmed: 22138650
Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature. 2006;444:840–6. https://doi.org/10.1038/nature05482
pubmed: 17167471
Kajimoto Y, Kaneto H. Role of oxidative stress in pancreatic beta-cell dysfunction. Ann N Y Acad Sci. 2004;1011:168–76. https://doi.org/10.1007/978-3-662-41088-2_17
pubmed: 15126294
Karaskov E, Scott C, Zhang L, Teodoro T, Ravazzola M, Volchuk A. Chronic palmitate but not oleate exposure induces endoplasmic reticulum stress, which may contribute to INS-1 pancreatic beta-cell apoptosis. Endocrinology. 2006;147:3398–407. https://doi.org/10.1210/en.2005-1494
pubmed: 16601139
Kato T, Shimano H, Yamamoto T, Ishikawa M, Kumadaki S, Matsuzaka T, Nakagawa Y, Yahagi N, Nakakuki M, Hasty AH, Takeuchi Y, Kobayashi K, Takahashi A, Yatoh S, Suzuki H, Sone H, Yamada N. Palmitate impairs and eicosapentaenoate restores insulin secretion through regulation of SREBP-1c in pancreatic islets. Diabetes. 2008;57:2382–92. https://doi.org/10.2337/db06-1806
pubmed: 18458149
pmcid: 2518489
Keane KN, Cruzat VF, Carlessi R, de Bittencourt PIH, Newsholme P. Molecular events linking oxidative stress and inflammation to insulin resistance and β-cell dysfunction. Oxidative Med Cell Longev. 2015;2015:181643. https://doi.org/10.1155/2015/181643
Kim AJ, Shi Y, Austin RC, Werstuck GH. Valproate protects cells from ER stress-induced lipid accumulation and apoptosis by inhibiting glycogen synthase kinase-3. J Cell Sci. 2005a;118:89–99. https://doi.org/10.1242/jcs.01562
pubmed: 15585578
Kim S-J, Winter K, Nian C, Tsuneoka M, Koda Y, McIntosh CHS. Glucose-dependent insulinotropic polypeptide (GIP) stimulation of pancreatic beta-cell survival is dependent upon phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB) signaling, inactivation of the forkhead transcription factor Foxo1, and down-regulation of bax expression. J Biol Chem. 2005b;280:22297–307. https://doi.org/10.1074/jbc.M500540200
pubmed: 15817464
Kim W-H, Lee JW, Suh YH, Lee HJ, Lee SH, Oh YK, Gao B, Jung MH. AICAR potentiates ROS production induced by chronic high glucose: roles of AMPK in pancreatic beta-cell apoptosis. Cell Signal. 2007;19:791–805. https://doi.org/10.1016/j.cellsig.2006.10.004
pubmed: 17127032
Kim MK, Jung HS, Yoon CS, Ko JH, Jun HJ, Kim TK, Kwon MJ, Lee SH, Ko KS, Rhee BD, Park JH. The effect of glucose fluctuation on apoptosis and function of INS-1 pancreatic Beta cells. Korean Diabetes J. 2010;34:47–54. https://doi.org/10.4093/kdj.2010.34.1.47
pubmed: 20532020
pmcid: 2879902
Kim M-H, Kim E-H, Jung HS, Yang D, Park E-Y, Jun H-S. EX4 stabilizes and activates Nrf2 via PKCδ, contributing to the prevention of oxidative stress-induced pancreatic beta cell damage. Toxicol Appl Pharmacol. 2017;315:60–9. https://doi.org/10.1016/j.taap.2016.12.005
pubmed: 27939242
Kitamura T, Ido Kitamura Y. Role of FoxO proteins in pancreatic beta cells. Endocr J. 2007;54:507–15. https://doi.org/10.1507/endocrj.kr-109
pubmed: 17510498
Klune JR, Dhupar R, Cardinal J, Billiar TR, Tsung A. HMGB1: endogenous danger signaling. Mol Med. 2008;14:476–84. https://doi.org/10.2119/2008-00034.Klune
pubmed: 18431461
pmcid: 2323334
Krokowski D, Han J, Saikia M, Majumder M, Yuan CL, Guan B-J, Bevilacqua E, Bussolati O, Bröer S, Arvan P, Tchórzewski M, Snider MD, Puchowicz M, Croniger CM, Kimball SR, Pan T, Koromilas AE, Kaufman RJ, Hatzoglou M. A self-defeating anabolic program leads to β-cell apoptosis in endoplasmic reticulum stress-induced diabetes via regulation of amino acid flux. J Biol Chem. 2013;288:17202–13. https://doi.org/10.1074/jbc.M113.466920
pubmed: 23645676
pmcid: 3682525
Lai E, Bikopoulos G, Wheeler MB, Rozakis-Adcock M, Volchuk A. Differential activation of ER stress and apoptosis in response to chronically elevated free fatty acids in pancreatic β-cells. Am J Physiol Endocrinol Metab. 2008;294:E540–50. https://doi.org/10.1152/ajpendo.00478.2007
Lanuza-Masdeu J, Arévalo MI, Vila C, Barberà A, Gomis R, Caelles C. In vivo JNK activation in pancreatic β-cells leads to glucose intolerance caused by insulin resistance in pancreas. Diabetes. 2013;62:2308–17. https://doi.org/10.2337/db12-1097
pubmed: 23349497
pmcid: 3712047
Law E, Lu S, Kieffer TJ, Warnock GL, Ao Z, Woo M, Marzban L. Differences between amyloid toxicity in alpha and beta cells in human and mouse islets and the role of caspase-3. Diabetologia. 2010;53:1415–27. https://doi.org/10.1007/s00125-010-1717-9
pubmed: 20369225
Le Marchand-Brustel Y, Gual P, Grémeaux T, Gonzalez T, Barrès R, Tanti J-F. Fatty acid-induced insulin resistance: role of insulin receptor substrate 1 serine phosphorylation in the retroregulation of insulin signalling. Biochem Soc Trans. 2003;31:1152–6. https://doi.org/10.1042/bst0311152 .
doi: 10.1042/bst0311152
pubmed: 14641015
Lee CS, Sund NJ, Vatamaniuk MZ, Matschinsky FM, Stoffers DA, Kaestner KH. Foxa2 controls Pdx1 gene expression in pancreatic β-cells in vivo. Diabetes. 2002;51:2546–51. https://doi.org/10.2337/diabetes.51.8.2546
Lee S-M, Choi S-E, Lee J-H, Lee J-J, Jung I-R, Lee S-J, Lee K-W, Kang Y. Involvement of the TLR4 (Toll-like receptor4) signaling pathway in palmitate-induced INS-1 beta cell death. Mol Cell Biochem. 2011;354:207–17. https://doi.org/10.1007/s11010-011-0820-7
pubmed: 21503675
Liang J, Wu SY, Zhang D, Wang L, Leung KK, Leung PS. NADPH oxidase-dependent reactive oxygen species stimulate β-cell regeneration through differentiation of endocrine progenitors in murine pancreas. Antioxid Redox Signal. 2016;24:419–33. https://doi.org/10.1089/ars.2014.6135
pubmed: 26464216
Lim S, Rashid MA, Jang M, Kim Y, Won H, Lee J, Woo J, Kim YS, Murphy MP, Ali L, Ha J, Kim SS. Mitochondria-targeted antioxidants protect pancreatic β-cells against oxidative stress and improve insulin secretion in glucotoxicity and glucolipotoxicity. Cell Physiol Biochem. 2011;28:873–86. https://doi.org/10.1159/000335802
pubmed: 22178940
Lingohr MK, Dickson LM, McCuaig JF, Hugl SR, Twardzik DR, Rhodes CJ. Activation of IRS-2-mediated signal transduction by IGF-1, but not TGF-alpha or EGF, augments pancreatic beta-cell proliferation. Diabetes. 2002;51:966–76. https://doi.org/10.2337/diabetes.51.4.966
pubmed: 11916914
Lingohr MK, Briaud I, Dickson LM, McCuaig JF, Alárcon C, Wicksteed BL, Rhodes CJ. Specific regulation of IRS-2 expression by glucose in rat primary pancreatic islet β-cells. J Biol Chem. 2006;281:15884–92. https://doi.org/10.1074/jbc.M600356200
Lipson KL, Fonseca SG, Ishigaki S, Nguyen LX, Foss E, Bortell R, Rossini AA, Urano F. Regulation of insulin biosynthesis in pancreatic beta cells by an endoplasmic reticulum-resident protein kinase IRE1. Cell Metab. 2006;4:245–54. https://doi.org/10.1016/j.cmet.2006.07.007 .
doi: 10.1016/j.cmet.2006.07.007
pubmed: 16950141
Liu C, Feng X, Li Q, Wang Y, Li Q, Hua M. Adiponectin, TNF-α and inflammatory cytokines and risk of type 2 diabetes: a systematic review and meta-analysis. Cytokine. 2016;86:100–9. https://doi.org/10.1016/j.cyto.2016.06.028
pubmed: 27498215
Liu C, Huang Y, Zhang Y, Chen X, Kong X, Dong Y. Intracellular methylglyoxal induces oxidative damage to pancreatic beta cell line INS-1 cell through Ire1α-JNK and mitochondrial apoptotic pathway. Free Radic Res. 2017;51:337–50. https://doi.org/10.1080/10715762.2017.1289376
pubmed: 28488455
Lizcano JM, Göransson O, Toth R, Deak M, Morrice NA, Boudeau J, Hawley SA, Udd L, Mäkelä TP, Hardie DG, Alessi DR. LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1. EMBO J. 2004;23:833–43. https://doi.org/10.1038/sj.emboj.7600110
pubmed: 14976552
pmcid: 381014
Lopes DHJ, Meister A, Gohlke A, Hauser A, Blume A, Winter R. Mechanism of islet amyloid polypeptide fibrillation at lipid interfaces studied by infrared reflection absorption spectroscopy. Biophys J. 2007;93:3132–41. https://doi.org/10.1529/biophysj.107.110635
pubmed: 17660321
pmcid: 2025658
Lupi R, Dotta F, Marselli L, Del Guerra S, Masini M, Santangelo C, Patané G, Boggi U, Piro S, Anello M, Bergamini E, Mosca F, Di Mario U, Del Prato S, Marchetti P. Prolonged exposure to free fatty acids has cytostatic and pro-apoptotic effects on human pancreatic islets: evidence that beta-cell death is caspase mediated, partially dependent on ceramide pathway, and Bcl-2 regulated. Diabetes. 2002;51:1437–42. https://doi.org/10.2337/diabetes.51.5.1437
pubmed: 11978640
Ly LD, Xu S, Choi S-K, Ha C-M, Thoudam T, Cha S-K, Wiederkehr A, Wollheim CB, Lee I-K, Park K-S. Oxidative stress and calcium dysregulation by palmitate in type 2 diabetes. Exp Mol Med. 2017;49:e291. https://doi.org/10.1038/emm.2016.157
pubmed: 28154371
pmcid: 5336562
Ma L, Zheng J. Single-cell gene expression analysis reveals β-cell dysfunction and deficit mechanisms in type 2 diabetes. BMC Bioinformatics. 2018;19:515. https://doi.org/10.1186/s12859-018-2519-1
pubmed: 30598071
pmcid: 6311914
Maedler K, Spinas GA, Lehmann R, Sergeev P, Weber M, Fontana A, Kaiser N, Donath MY. Glucose induces beta-cell apoptosis via upregulation of the Fas receptor in human islets. Diabetes. 2001;50:1683–90. https://doi.org/10.2337/diabetes.50.8.1683
pubmed: 11473025
Maedler K, Fontana A, Ris F, Sergeev P, Toso C, Oberholzer J, Lehmann R, Bachmann F, Tasinato A, Spinas GA, Halban PA, Donath MY. FLIP switches Fas-mediated glucose signaling in human pancreatic beta cells from apoptosis to cell replication. Proc Natl Acad Sci U S A. 2002;99:8236–41. https://doi.org/10.1073/pnas.122686299
pubmed: 12060768
pmcid: 123051
Maedler K, Sergeev P, Ehses JA, Mathe Z, Bosco D, Berney T, Dayer J-M, Reinecke M, Halban PA, Donath MY. Leptin modulates beta cell expression of IL-1 receptor antagonist and release of IL-1beta in human islets. Proc Natl Acad Sci U S A. 2004;101:8138–43. https://doi.org/10.1073/pnas.0305683101
pubmed: 15141093
pmcid: 419570
Maedler K, Schulthess FT, Bielman C, Berney T, Bonny C, Prentki M, Donath MY, Roduit R. Glucose and leptin induce apoptosis in human β-cells and impair glucose-stimulated insulin secretion through activation of c-Jun N-terminal kinases. FASEB J. 2008;22:1905–13. https://doi.org/10.1096/fj.07-101824
Martinez SC, Tanabe K, Cras-Méneur C, Abumrad NA, Bernal-Mizrachi E, Permutt MA. Inhibition of Foxo1 protects pancreatic islet β-cells against fatty acid and endoplasmic reticulum stress-induced apoptosis. Diabetes. 2008;57:846–59. https://doi.org/10.2337/db07-0595
Matschinsky FM. Assessing the potential of glucokinase activators in diabetes therapy. Nat Rev Drug Discov. 2009;8:399–416. https://doi.org/10.1038/nrd2850
pubmed: 19373249
Matsuoka T, Artner I, Henderson E, Means A, Sander M, Stein R. The MafA transcription factor appears to be responsible for tissue-specific expression of insulin. Proc Natl Acad Sci U S A. 2004;101:2930–3. https://doi.org/10.1073/pnas.0306233101
pubmed: 14973194
pmcid: 365722
Matsuoka T, Kaneto H, Kawashima S, Miyatsuka T, Tochino Y, Yoshikawa A, Imagawa A, Miyazaki J, Gannon M, Stein R, Shimomura I. Preserving Mafa expression in diabetic islet β-cells improves glycemic control in vivo. J Biol Chem. 2015;290:7647–57. https://doi.org/10.1074/jbc.M114.595579
pubmed: 25645923
pmcid: 4367268
Matsuoka T-A, Kawashima S, Miyatsuka T, Sasaki S, Shimo N, Katakami N, Kawamori D, Takebe S, Herrera PL, Kaneto H, Stein R, Shimomura I. Mafa enables Pdx1 to effectively convert pancreatic islet progenitors and committed islet α-cells into β-cells in vivo. Diabetes. 2017;66:1293–300. https://doi.org/10.2337/db16-0887
pubmed: 28223284
pmcid: 5399608
McKenzie MD, Carrington EM, Kaufmann T, Strasser A, Huang DCS, Kay TWH, Allison J, Thomas HE. Proapoptotic BH3-only protein bid is essential for death receptor-induced apoptosis of pancreatic β-cells. Diabetes. 2008;57:1284–92. https://doi.org/10.2337/db07-1692
McKenzie MD, Jamieson E, Jansen ES, Scott CL, Huang DCS, Bouillet P, Allison J, Kay TWH, Strasser A, Thomas HE. Glucose induces pancreatic islet cell apoptosis that requires the BH3-only proteins Bim and Puma and multi-BH domain protein Bax. Diabetes. 2010;59:644–52. https://doi.org/10.2337/db09-1151
pubmed: 19959756
Meier JJ, Pennartz C, Schenker N, Menge BA, Schmidt WE, Heise T, Kapitza C, Veldhuis JD. Hyperglycaemia is associated with impaired pulsatile insulin secretion: effect of basal insulin therapy. Diabetes Obes Metab. 2013;15:258–63. https://doi.org/10.1111/dom.12022
pubmed: 23039360
Meng Z, Lv J, Luo Y, Lin Y, Zhu Y, Nie J, Yang T, Sun Y, Han X. Forkhead box O1/pancreatic and duodenal homeobox 1 intracellular translocation is regulated by c-Jun N-terminal kinase and involved in prostaglandin E2-induced pancreatic beta-cell dysfunction. Endocrinology. 2009;150:5284–93. https://doi.org/10.1210/en.2009-0671
pubmed: 19837872
Meyerovich K, Fukaya M, Terra LF, Ortis F, Eizirik DL, Cardozo AK. The non-canonical NF-κB pathway is induced by cytokines in pancreatic beta cells and contributes to cell death and proinflammatory responses in vitro. Diabetologia. 2016;59:512–21. https://doi.org/10.1007/s00125-015-3817-z
pubmed: 26634571
Mihailidou C, Papavassiliou AG, Kiaris H. A crosstalk between p21 and UPR-induced transcription factor C/EBP homologous protein (CHOP) linked to type 2 diabetes. Biochimie. 2014;99:19–27. https://doi.org/10.1016/j.biochi.2013.11.003
pubmed: 24239558
Mihailidou C, Chatzistamou I, Papavassiliou AG, Kiaris H. Regulation of P21 during diabetes-associated stress of the endoplasmic reticulum. Endocr Relat Cancer. 2015;22:217–28. https://doi.org/10.1530/ERC-15-0018
pubmed: 25670031
Mirzabekov TA, Lin MC, Kagan BL. Pore formation by the cytotoxic islet amyloid peptide amylin. J Biol Chem. 1996;271:1988–92. https://doi.org/10.1074/jbc.271.4.1988
pubmed: 8567648
Miyazaki S, Minamida R, Furuyama T, Tashiro F, Yamato E, Inagaki S, Miyazaki J. Analysis of Foxo1-regulated genes using Foxo1-deficient pancreatic β-cells. Genes Cells. 2012;17:758–67. https://doi.org/10.1111/j.1365-2443.2012.01625.x
Morgan NG, Dhayal S. Unsaturated fatty acids as cytoprotective agents in the pancreatic beta-cell. Prostaglandins Leukot Essent Fatty Acids. 2010;82:231–6. https://doi.org/10.1016/j.plefa.2010.02.018
pubmed: 20206490
Morgan D, Oliveira-Emilio HR, Keane D, Hirata AE, Santos da Rocha M, Bordin S, Curi R, Newsholme P, Carpinelli AR. Glucose, palmitate and pro-inflammatory cytokines modulate production and activity of a phagocyte-like NADPH oxidase in rat pancreatic islets and a clonal beta cell line. Diabetologia. 2007;50:359–69. https://doi.org/10.1007/s00125-006-0462-6
pubmed: 17151863
Musashi M, Ota S, Shiroshita N. The role of protein kinase C isoforms in cell proliferation and apoptosis. Int J Hematol. 2000;72:12–9.
pubmed: 10979203
Nakamura A, Togashi Y, Orime K, Sato K, Shirakawa J, Ohsugi M, Kubota N, Kadowaki T, Terauchi Y. Control of beta cell function and proliferation in mice stimulated by small-molecule glucokinase activator under various conditions. Diabetologia. 2012;55:1745–54. https://doi.org/10.1007/s00125-012-2521-5
pubmed: 22456697
Newsholme P, Haber EP, Hirabara SM, Rebelato ELO, Procopio J, Morgan D, Oliveira-Emilio HC, Carpinelli AR, Curi R. Diabetes associated cell stress and dysfunction: role of mitochondrial and non-mitochondrial ROS production and activity. J Physiol Lond. 2007;583:9–24. https://doi.org/10.1113/jphysiol.2007.135871
pubmed: 17584843
pmcid: 2277225
Nguyen T, Sherratt PJ, Pickett CB. Regulatory mechanisms controlling gene expression mediated by the antioxidant response element. Annu Rev Pharmacol Toxicol. 2003;43:233–60. https://doi.org/10.1146/annurev.pharmtox.43.100901.140229
pubmed: 12359864
Nishi M, Sanke T, Nagamatsu S, Bell GI, Steiner DF. Islet amyloid polypeptide. A new beta cell secretory product related to islet amyloid deposits. J Biol Chem. 1990;265:4173–6.
pubmed: 2407732
Nishitoh H, Saitoh M, Mochida Y, Takeda K, Nakano H, Rothe M, Miyazono K, Ichijo H. ASK1 is essential for JNK/SAPK activation by TRAF2. Mol Cell. 1998;2:389–95. https://doi.org/10.1016/s1097-2765(00)80283-x
pubmed: 9774977
Nishizuka Y. Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. Science. 1992;258:607–14. https://doi.org/10.1126/science.1411571
pubmed: 1411571
Norlin S, Ahlgren U, Edlund H. Nuclear factor-{kappa}B activity in {beta}-cells is required for glucose-stimulated insulin secretion. Diabetes. 2005;54:125–32. https://doi.org/10.2337/diabetes.54.1.125
pubmed: 15616019
Nowotny K, Jung T, Höhn A, Weber D, Grune T. Advanced glycation end products and oxidative stress in type 2 diabetes mellitus. Biomol Ther. 2015;5:194–222. https://doi.org/10.3390/biom5010194
Offield MF, Jetton TL, Labosky PA, Ray M, Stein RW, Magnuson MA, Hogan BL, Wright CV. PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenum. Development. 1996;122:983–95.
pubmed: 8631275
Oh YS, Lee Y-J, Park K, Choi HH, Yoo S, Jun H-S. Treatment with glucokinase activator, YH-GKA, increases cell proliferation and decreases glucotoxic apoptosis in INS-1 cells. Eur J Pharm Sci. 2014;51:137–45. https://doi.org/10.1016/j.ejps.2013.09.005
pubmed: 24056026
Oslowski CM, Urano F. The binary switch that controls the life and death decisions of ER stressed β-cells. Curr Opin Cell Biol. 2011;23:207–15. https://doi.org/10.1016/j.ceb.2010.11.005
Oyadomari S, Koizumi A, Takeda K, Gotoh T, Akira S, Araki E, Mori M. Targeted disruption of the chop gene delays endoplasmic reticulum stress-mediated diabetes. J Clin Invest. 2002;109:525–32. https://doi.org/10.1172/JCI14550
pubmed: 11854325
pmcid: 150879
Papizan JB, Singer RA, Tschen S-I, Dhawan S, Friel JM, Hipkens SB, Magnuson MA, Bhushan A, Sussel L. Nkx2.2 repressor complex regulates islet β-cell specification and prevents β-to-α-cell reprogramming. Genes Dev. 2011;25:2291–305. https://doi.org/10.1101/gad.173039.111
pubmed: 22056672
pmcid: 3219233
Park JS, Arcaroli J, Yum H-K, Yang H, Wang H, Yang K-Y, Choe K-H, Strassheim D, Pitts TM, Tracey KJ, Abraham E. Activation of gene expression in human neutrophils by high mobility group box 1 protein. Am J Physiol Cell Physiol. 2003;284:C870–9. https://doi.org/10.1152/ajpcell.00322.2002
pubmed: 12620891
Park YJ, Lee S, Kieffer TJ, Warnock GL, Safikhan N, Speck M, Hao Z, Woo M, Marzban L. Deletion of Fas protects islet beta cells from cytotoxic effects of human islet amyloid polypeptide. Diabetologia. 2012; https://doi.org/10.1007/s00125-012-2451-2
Park YJ, Woo M, Kieffer TJ, Hakem R, Safikhan N, Yang F, Ao Z, Warnock GL, Marzban L. The role of caspase-8 in amyloid-induced beta cell death in human and mouse islets. Diabetologia. 2014;57:765–75. https://doi.org/10.1007/s00125-013-3152-1
pubmed: 24442508
Park YJ, Warnock GL, Ao Z, Safikhan N, Meloche M, Asadi A, Kieffer TJ, Marzban L. Dual role of interleukin-1β in islet amyloid formation and its β-cell toxicity: implications for type 2 diabetes and islet transplantation. Diabetes Obes Metab. 2017;19:682–94. https://doi.org/10.1111/dom.12873
pubmed: 28058779
Paulsson JF, Andersson A, Westermark P, Westermark GT. Intracellular amyloid-like deposits contain unprocessed pro-islet amyloid polypeptide (proIAPP) in beta cells of transgenic mice overexpressing the gene for human IAPP and transplanted human islets. Diabetologia. 2006;49:1237–46. https://doi.org/10.1007/s00125-006-0206-7
pubmed: 16570161
Pavitt GD, Ron D. New insights into translational regulation in the endoplasmic reticulum unfolded protein response. Cold Spring Harb Perspect Biol. 2012;4. https://doi.org/10.1101/cshperspect.a012278
Pi J, Bai Y, Zhang Q, Wong V, Floering LM, Daniel K, Reece JM, Deeney JT, Andersen ME, Corkey BE, Collins S. Reactive oxygen species as a signal in glucose-stimulated insulin secretion. Diabetes. 2007;56:1783–91. https://doi.org/10.2337/db06-1601
pubmed: 17400930
Pi J, Zhang Q, Fu J, Woods CG, Hou Y, Corkey BE, Collins S, Andersen ME. ROS signaling, oxidative stress and Nrf2 in pancreatic beta-cell function. Toxicol Appl Pharmacol. 2010;244:77–83. https://doi.org/10.1016/j.taap.2009.05.025
pubmed: 19501608
Pirot P, Ortis F, Cnop M, Ma Y, Hendershot LM, Eizirik DL, Cardozo AK. Transcriptional regulation of the endoplasmic reticulum stress gene chop in pancreatic insulin-producing cells. Diabetes. 2007;56:1069–77. https://doi.org/10.2337/db06-1253
pubmed: 17395747
Poitout V, Amyot J, Semache M, Zarrouki B, Hagman D, Fontés G. Glucolipotoxicity of the pancreatic beta cell. Biochim Biophys Acta. 2010;1801:289–98. https://doi.org/10.1016/j.bbalip.2009.08.006
pubmed: 19715772
Qin J, Fang N, Lou J, Zhang W, Xu S, Liu H, Fang Q, Wang Z, Liu J, Men X, Peng L, Chen L. TRB3 is involved in free fatty acid-induced INS-1-derived cell apoptosis via the protein kinase C δ pathway. PLoS One. 2014;9:e96089. https://doi.org/10.1371/journal.pone.0096089
pubmed: 24824999
pmcid: 4019472
Qiu Y, Mao T, Zhang Y, Shao M, You J, Ding Q, Chen Y, Wu D, Xie D, Lin X, Gao X, Kaufman RJ, Li W, Liu Y. A crucial role for RACK1 in the regulation of glucose-stimulated IRE1alpha activation in pancreatic beta cells. Sci Signal. 2010;3:ra7. https://doi.org/10.1126/scisignal.2000514
pubmed: 20103773
pmcid: 2940714
Quan W, Jo E-K, Lee M-S. Role of pancreatic β-cell death and inflammation in diabetes. Diabetes Obes Metab. 2013;15(Suppl 3):141–51. https://doi.org/10.1111/dom.12153
pubmed: 24003931
Rabhi N, Salas E, Froguel P, Annicotte J-S. Role of the unfolded protein response in β-cell compensation and failure during diabetes. J Diabetes Res. 2014;2014:795171. https://doi.org/10.1155/2014/795171
Rahier J, Guiot Y, Goebbels RM, Sempoux C, Henquin JC. Pancreatic beta-cell mass in European subjects with type 2 diabetes. Diabetes Obes Metab. 2008;10(Suppl 4):32–42. https://doi.org/10.1111/j.1463-1326.2008.00969.x .
doi: 10.1111/j.1463-1326.2008.00969.x
pubmed: 18834431
Rehman K, Akash MSH. Mechanisms of inflammatory responses and development of insulin resistance: how are they interlinked? J Biomed Sci. 2016;23:87. https://doi.org/10.1186/s12929-016-0303-y
pubmed: 27912756
pmcid: 5135788
Rehman K, Akash MSH. Mechanism of generation of oxidative stress and pathophysiology of type 2 diabetes mellitus: how are they interlinked? J Cell Biochem. 2017;118:3577–85. https://doi.org/10.1002/jcb.26097
pubmed: 28460155
Reyland ME. Protein kinase Cdelta and apoptosis. Biochem Soc Trans. 2007;35:1001–4. https://doi.org/10.1042/BST0351001
pubmed: 17956263
Rhodes CJ. Type 2 diabetes-a matter of beta-cell life and death? Science. 2005;307:380–4. https://doi.org/10.1126/science.1104345
pubmed: 15662003
Rieck S, Kaestner KH. Expansion of beta-cell mass in response to pregnancy. Trends Endocrinol Metab. 2010;21:151–8. https://doi.org/10.1016/j.tem.2009.11.001
pubmed: 20015659
Rivera JF, Gurlo T, Daval M, Huang CJ, Matveyenko AV, Butler PC, Costes S. Human-IAPP disrupts the autophagy/lysosomal pathway in pancreatic β-cells: protective role of p62-positive cytoplasmic inclusions. Cell Death Differ. 2011;18:415–26. https://doi.org/10.1038/cdd.2010.111
pubmed: 20814419
Robertson RP, Harmon J, Tran PO, Tanaka Y, Takahashi H. Glucose toxicity in β-cells: type 2 diabetes, good radicals gone bad, and the glutathione connection. Diabetes. 2003;52:581–7. https://doi.org/10.2337/diabetes.52.3.581
Robertson RP, Harmon J, Tran POT, Poitout V. Beta-cell glucose toxicity, lipotoxicity, and chronic oxidative stress in type 2 diabetes. Diabetes. 2004;53(Suppl 1):S119–24. https://doi.org/10.2337/diabetes.53.2007.s119 .
doi: 10.2337/diabetes.53.2007.s119
pubmed: 14749276
Robertson R, Zhou H, Zhang T, Harmon JS. Chronic oxidative stress as a mechanism for glucose toxicity of the beta cell in type 2 diabetes. Cell Biochem Biophys. 2007;48:139–46. https://doi.org/10.1007/s12013-007-0026-5
pubmed: 17709883
Roglic G, Unwin N. Mortality attributable to diabetes: estimates for the year 2010. Diabetes Res Clin Pract. 2010;87:15–9. https://doi.org/10.1016/j.diabres.2009.10.006
pubmed: 19914728
Ron D, Walter P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol. 2007;8:519–29. https://doi.org/10.1038/nrm2199
pubmed: 17565364
Rourke JL, Hu Q, Screaton RA. AMPK and friends: central regulators of β-cell biology. Trends Endocrinol Metab. 2018;29:111–22. https://doi.org/10.1016/j.tem.2017.11.007
Saini V. Molecular mechanisms of insulin resistance in type 2 diabetes mellitus. World J Diabetes. 2010;1:68–75. https://doi.org/10.4239/wjd.v1.i3.68
pubmed: 21537430
pmcid: 3083885
Sakai K, Matsumoto K, Nishikawa T, Suefuji M, Nakamaru K, Hirashima Y, Kawashima J, Shirotani T, Ichinose K, Brownlee M, Araki E. Mitochondrial reactive oxygen species reduce insulin secretion by pancreatic β-cells. Biochem Biophys Res Commun. 2003;300:216–22. https://doi.org/10.1016/s0006-291x(02)02832-2
Sander M, Neubüser A, Kalamaras J, Ee HC, Martin GR, German MS. Genetic analysis reveals that PAX6 is required for normal transcription of pancreatic hormone genes and islet development. Genes Dev. 1997;11:1662–73. https://doi.org/10.1101/gad.11.13.1662
pubmed: 9224716
Sander M, Sussel L, Conners J, Scheel D, Kalamaras J, Dela Cruz F, Schwitzgebel V, Hayes-Jordan A, German M. Homeobox gene Nkx6.1 lies downstream of Nkx2.2 in the major pathway of beta-cell formation in the pancreas. Development. 2000;127:5533–40.
pubmed: 11076772
Sano R, Reed JC. ER stress-induced cell death mechanisms. Biochim Biophys Acta. 2013;1833:3460–70. https://doi.org/10.1016/j.bbamcr.2013.06.028
pubmed: 23850759
Schalkwijk CG. Vascular AGE-ing by methylglyoxal: the past, the present and the future. Diabetologia. 2015;58:1715–9. https://doi.org/10.1007/s00125-015-3597-5
pubmed: 25962521
pmcid: 4499108
Scheuner D, Kaufman RJ. The unfolded protein response: a pathway that links insulin demand with beta-cell failure and diabetes. Endocr Rev. 2008;29:317–33. https://doi.org/10.1210/er.2007-0039
pubmed: 18436705
pmcid: 2528859
Schinner S, Scherbaum WA, Bornstein SR, Barthel A. Molecular mechanisms of insulin resistance. Diabet Med. 2005;22:674–82. https://doi.org/10.1111/j.1464-5491.2005.01566.x
pubmed: 15910615
Schwarz J-M, Linfoot P, Dare D, Aghajanian K. Hepatic de novo lipogenesis in normoinsulinemic and hyperinsulinemic subjects consuming high-fat, low-carbohydrate and low-fat, high-carbohydrate isoenergetic diets. Am J Clin Nutr. 2003;77:43–50. https://doi.org/10.1093/ajcn/77.1.43
pubmed: 12499321
Semache M, Zarrouki B, Fontés G, Fogarty S, Kikani C, Chawki MB, Rutter J, Poitout V. Per-Arnt-Sim kinase regulates pancreatic duodenal homeobox-1 protein stability via phosphorylation of glycogen synthase kinase 3β in pancreatic β-cells. J Biol Chem. 2013;288:24825–33. https://doi.org/10.1074/jbc.M113.495945
pubmed: 23853095
pmcid: 3750177
Shah OJ, Wang Z, Hunter T. Inappropriate activation of the TSC/Rheb/mTOR/S6K cassette induces IRS1/2 depletion, insulin resistance, and cell survival deficiencies. Curr Biol. 2004;14:1650–6. https://doi.org/10.1016/j.cub.2004.08.026
pubmed: 15380067
Shao S, Fang Z, Yu X, Zhang M. Transcription factors involved in glucose-stimulated insulin secretion of pancreatic beta cells. Biochem Biophys Res Commun. 2009;384:401–4. https://doi.org/10.1016/j.bbrc.2009.04.135
pubmed: 19410555
Shao S, Liu Z, Yang Y, Zhang M, Yu X. SREBP-1c, Pdx-1, and GLP-1R involved in palmitate-EPA regulated glucose-stimulated insulin secretion in INS-1 cells. J Cell Biochem. 2010;111:634–42. https://doi.org/10.1002/jcb.22750
pubmed: 20589757
Shao S, Yang Y, Yuan G, Zhang M, Yu X. Signaling molecules involved in lipid-induced pancreatic beta-cell dysfunction. DNA Cell Biol. 2013;32:41–9. https://doi.org/10.1089/dna.2012.1874
pubmed: 23347443
pmcid: 3557433
Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010;87:4–14. https://doi.org/10.1016/j.diabres.2009.10.007
pubmed: 19896746
Shigihara N, Fukunaka A, Hara A, Komiya K, Honda A, Uchida T, Abe H, Toyofuku Y, Tamaki M, Ogihara T, Miyatsuka T, Hiddinga HJ, Sakagashira S, Koike M, Uchiyama Y, Yoshimori T, Eberhardt NL, Fujitani Y, Watada H. Human IAPP-induced pancreatic β-cell toxicity and its regulation by autophagy. J Clin Invest. 2014;124:3634–44. https://doi.org/10.1172/JCI69866
Shirakawa J, Kulkarni RN. Novel factors modulating human β-cell proliferation. Diabetes Obes Metab. 2016;18(Suppl 1):71–7. https://doi.org/10.1111/dom.12731 .
doi: 10.1111/dom.12731
pubmed: 27615134
pmcid: 5021183
Shirakawa J, Togashi Y, Sakamoto E, Kaji M, Tajima K, Orime K, Inoue H, Kubota N, Kadowaki T, Terauchi Y. Glucokinase activation ameliorates ER stress-induced apoptosis in pancreatic β-cells. Diabetes. 2013;62:3448–58. https://doi.org/10.2337/db13-0052
pubmed: 23801577
pmcid: 3781485
Sidarala V, Veluthakal R, Syeda K, Vlaar C, Newsholme P, Kowluru A. Phagocyte-like NADPH oxidase (Nox2) promotes activation of p38MAPK in pancreatic β-cells under glucotoxic conditions: evidence for a requisite role of Ras-related C3 botulinum toxin substrate 1 (Rac1). Biochem Pharmacol. 2015;95:301–10. https://doi.org/10.1016/j.bcp.2015.04.001
pubmed: 25881746
pmcid: 6684092
Simon-Szabó L, Kokas M, Mandl J, Kéri G, Csala M. Metformin attenuates palmitate-induced endoplasmic reticulum stress, serine phosphorylation of IRS-1 and apoptosis in rat insulinoma cells. PLoS One. 2014;9:e97868. https://doi.org/10.1371/journal.pone.0097868
pubmed: 24896641
pmcid: 4045581
Sosa-Pineda B, Chowdhury K, Torres M, Oliver G, Gruss P. The Pax4 gene is essential for differentiation of insulin-producing beta cells in the mammalian pancreas. Nature. 1997;386:399–402. https://doi.org/10.1038/386399a0
pubmed: 9121556
Šrámek J, Němcová-Fürstová V, Kovář J. Kinase signaling in apoptosis induced by saturated fatty acids in pancreatic β-cells. Int J Mol Sci. 2016;17. https://doi.org/10.3390/ijms17091400
Srinivasan S, Ohsugi M, Liu Z, Fatrai S, Bernal-Mizrachi E, Permutt MA. Endoplasmic reticulum stress-induced apoptosis is partly mediated by reduced insulin signaling through phosphatidylinositol 3-kinase/Akt and increased glycogen synthase kinase-3beta in mouse insulinoma cells. Diabetes. 2005;54:968–75. https://doi.org/10.2337/diabetes.54.4.968
pubmed: 15793234
Stassi G, De Maria R, Trucco G, Rudert W, Testi R, Galluzzo A, Giordano C, Trucco M. Nitric oxide primes pancreatic beta cells for Fas-mediated destruction in insulin-dependent diabetes mellitus. J Exp Med. 1997;186:1193–200. https://doi.org/10.1084/jem.186.8.1193
pubmed: 9334358
pmcid: 2199078
Stephens LA, Thomas HE, Ming L, Grell M, Darwiche R, Volodin L, Kay TW. Tumor necrosis factor-alpha-activated cell death pathways in NIT-1 insulinoma cells and primary pancreatic beta cells. Endocrinology. 1999;140:3219–27. https://doi.org/10.1210/endo.140.7.6873
pubmed: 10385418
Subramanian SL, Hull RL, Zraika S, Aston-Mourney K, Udayasankar J, Kahn SE. cJUN N-terminal kinase (JNK) activation mediates islet amyloid-induced beta cell apoptosis in cultured human islet amyloid polypeptide transgenic mouse islets. Diabetologia. 2012;55:166–74. https://doi.org/10.1007/s00125-011-2338-7
pubmed: 22038516
Sun G, Tarasov AI, McGinty JA, French PM, McDonald A, Leclerc I, Rutter GA. LKB1 deletion with the RIP2.Cre transgene modifies pancreatic beta-cell morphology and enhances insulin secretion in vivo. Am J Physiol Endocrinol Metab. 2010;298:E1261–73. https://doi.org/10.1152/ajpendo.00100.2010
pubmed: 20354156
pmcid: 2886523
Swisa A, Granot Z, Tamarina N, Sayers S, Bardeesy N, Philipson L, Hodson DJ, Wikstrom JD, Rutter GA, Leibowitz G, Glaser B, Dor Y. Loss of liver kinase B1 (LKB1) in Beta cells enhances glucose-stimulated insulin secretion despite profound mitochondrial defects. J Biol Chem. 2015;290:20934–46. https://doi.org/10.1074/jbc.M115.639237
pubmed: 26139601
pmcid: 4543653
Szabadkai G, Duchen MR. Mitochondria mediated cell death in diabetes. Apoptosis. 2009;14:1405–23. https://doi.org/10.1007/s10495-009-0363-5
pubmed: 19466549
Takamoto I, Terauchi Y, Kubota N, Ohsugi M, Ueki K, Kadowaki T. Crucial role of insulin receptor substrate-2 in compensatory beta-cell hyperplasia in response to high fat diet-induced insulin resistance. Diabetes Obes Metab. 2008;10(Suppl 4):147–56. https://doi.org/10.1111/j.1463-1326.2008.00951.x .
doi: 10.1111/j.1463-1326.2008.00951.x
pubmed: 18834442
Talchai C, Xuan S, Lin HV, Sussel L, Accili D. Pancreatic β-cell dedifferentiation as a mechanism of diabetic β-cell failure. Cell. 2012;150:1223–34. https://doi.org/10.1016/j.cell.2012.07.029
Tamura K, Minami K, Kudo M, Iemoto K, Takahashi H, Seino S. Liraglutide improves pancreatic Beta cell mass and function in alloxan-induced diabetic mice. PLoS One. 2015;10:e0126003. https://doi.org/10.1371/journal.pone.0126003
pubmed: 25938469
pmcid: 4418765
Taylor R. Type 2 diabetes: etiology and reversibility. Diabetes Care. 2013;36:1047–55. https://doi.org/10.2337/dc12-1805
pubmed: 23520370
pmcid: 3609491
Taylor R. Calorie restriction and reversal of type 2 diabetes. Expert Rev Endocrinol Metab. 2016;11:521–8. https://doi.org/10.1080/17446651.2016.1239525
pubmed: 30058916
Taylor R. Putting insulin resistance into context by dietary reversal of type 2 diabetes. J R Coll Physicians Edinb. 2017;47:168–71. https://doi.org/10.4997/JRCPE.2017.216
pubmed: 28675193
Terauchi Y, Takamoto I, Kubota N, Matsui J, Suzuki R, Komeda K, Hara A, Toyoda Y, Miwa I, Aizawa S, Tsutsumi S, Tsubamoto Y, Hashimoto S, Eto K, Nakamura A, Noda M, Tobe K, Aburatani H, Nagai R, Kadowaki T. Glucokinase and IRS-2 are required for compensatory beta cell hyperplasia in response to high-fat diet-induced insulin resistance. J Clin Invest. 2007;117:246–57. https://doi.org/10.1172/JCI17645
pubmed: 17200721
pmcid: 1716196
Thorel F, Népote V, Avril I, Kohno K, Desgraz R, Chera S, Herrera PL. Conversion of adult pancreatic alpha-cells to β-cells after extreme beta-cell loss. Nature. 2010;464:1149–54. https://doi.org/10.1038/nature08894 .
Tong HV, Luu NK, Son HA, Hoan NV, Hung TT, Velavan TP, Toan NL. Adiponectin and pro-inflammatory cytokines are modulated in Vietnamese patients with type 2 diabetes mellitus. J Diabetes Investig. 2017;8:295–305. https://doi.org/10.1111/jdi.12579
pubmed: 27684566
Tournier C, Dong C, Turner TK, Jones SN, Flavell RA, Davis RJ. MKK7 is an essential component of the JNK signal transduction pathway activated by proinflammatory cytokines. Genes Dev. 2001;15:1419–26. https://doi.org/10.1101/gad.888501 .
doi: 10.1101/gad.888501
pubmed: 11390361
pmcid: 312702
Tsunekawa S, Demozay D, Briaud I, McCuaig J, Accili D, Stein R, Rhodes CJ. FoxO feedback control of basal IRS-2 expression in pancreatic β-cells is distinct from that in hepatocytes. Diabetes. 2011;60:2883–91. https://doi.org/10.2337/db11-0340
pubmed: 21933986
pmcid: 3198101
Urano F, Wang X, Bertolotti A, Zhang Y, Chung P, Harding HP, Ron D. Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science. 2000;287:664–6. https://doi.org/10.1126/science.287.5453.664
pubmed: 10650002
van Vliet AR, Agostinis P. Mitochondria-associated membranes and ER stress. Curr Top Microbiol Immunol. 2018;414:73–102. https://doi.org/10.1007/82_2017_2 .
doi: 10.1007/82_2017_2
pubmed: 28349285
Wali JA, Masters SL, Thomas HE. Linking metabolic abnormalities to apoptotic pathways in Beta cells in type 2 diabetes. Cell. 2013;2:266–83. https://doi.org/10.3390/cells2020266
Wang C-H, Wei Y-H. Role of mitochondrial dysfunction and dysregulation of Ca2+ homeostasis in the pathophysiology of insulin resistance and type 2 diabetes. J Biomed Sci. 2017;24:70. https://doi.org/10.1186/s12929-017-0375-3
pubmed: 28882140
pmcid: 5588717
Wang IX, Ramrattan G, Cheung VG. Genetic variation in insulin-induced kinase signaling. Mol Syst Biol. 2015;11:820. https://doi.org/10.15252/msb.20156250
pubmed: 26202599
pmcid: 4547848
Wang Y, Zhong J, Zhang X, Liu Z, Yang Y, Gong Q, Ren B. The role of HMGB1 in the pathogenesis of type 2 diabetes. J Diabetes Res. 2016;2016:2543268. https://doi.org/10.1155/2016/2543268
pubmed: 28101517
pmcid: 5215175
Wang W, Liu C, Jimenez-Gonzalez M, Song W-J, Hussain MA. The undoing and redoing of the diabetic β-cell. J Diabetes Complicat. 2017;31:912–7. https://doi.org/10.1016/j.jdiacomp.2017.01.028
pmcid: 5450161
Watson ML, Macrae K, Marley AE, Hundal HS. Chronic effects of palmitate overload on nutrient-induced insulin secretion and autocrine signalling in pancreatic MIN6 beta cells. PLoS One. 2011;6:e25975. https://doi.org/10.1371/journal.pone.0025975
pubmed: 21998735
pmcid: 3187833
Weaver JR, Grzesik W, Taylor-Fishwick DA. Inhibition of NADPH oxidase-1 preserves beta cell function. Diabetologia. 2015;58:113–21. https://doi.org/10.1007/s00125-014-3398-2
pubmed: 25277953
Wei P, Shi M, Barnum S, Cho H, Carlson T, Fraser JD. Effects of glucokinase activators GKA50 and LY2121260 on proliferation and apoptosis in pancreatic INS-1 beta cells. Diabetologia. 2009;52:2142–50. https://doi.org/10.1007/s00125-009-1446-0
pubmed: 19641898
Weir GC, Bonner-Weir S. Five stages of evolving beta-cell dysfunction during progression to diabetes. Diabetes. 2004;53(Suppl 3):S16–21. https://doi.org/10.2337/diabetes.53.suppl_3.s16
pubmed: 15561905
Weir GC, Aguayo-Mazzucato C, Bonner-Weir S. β-cell dedifferentiation in diabetes is important, but what is it? Islets. 2013;5:233–7. https://doi.org/10.4161/isl.27494
pubmed: 24356710
pmcid: 4010577
Westermark P, Andersson A, Westermark GT. Islet amyloid polypeptide, islet amyloid, and diabetes mellitus. Physiol Rev. 2011;91:795–826. https://doi.org/10.1152/physrev.00042.2009
pubmed: 21742788
Westwell-Roper C, Dai DL, Soukhatcheva G, Potter KJ, van Rooijen N, Ehses JA, Verchere CB. IL-1 blockade attenuates islet amyloid polypeptide-induced proinflammatory cytokine release and pancreatic islet graft dysfunction. J Immunol. 2011;187:2755–65. https://doi.org/10.4049/jimmunol.1002854
pubmed: 21813778
Westwell-Roper C, Nackiewicz D, Dan M, Ehses JA. Toll-like receptors and NLRP3 as central regulators of pancreatic islet inflammation in type 2 diabetes. Immunol Cell Biol. 2014;92:314–23. https://doi.org/10.1038/icb.2014.4
pubmed: 24492799
White MF. IRS proteins and the common path to diabetes. Am J Physiol Endocrinol Metab. 2002;283:E413–22. https://doi.org/10.1152/ajpendo.00514.2001
pubmed: 12169433
Whitmarsh AJ, Kuan CY, Kennedy NJ, Kelkar N, Haydar TF, Mordes JP, Appel M, Rossini AA, Jones SN, Flavell RA, Rakic P, Davis RJ. Requirement of the JIP1 scaffold protein for stress-induced JNK activation. Genes Dev. 2001;15:2421–32. https://doi.org/10.1101/gad.922801 .
doi: 10.1101/gad.922801
pubmed: 11562351
pmcid: 312784
Wilcox CL, Terry NA, Walp ER, Lee RA, May CL. Pancreatic α-cell specific deletion of mouse Arx leads to α-cell identity loss. PLoS One. 2013;8:e66214. https://doi.org/10.1371/journal.pone.0066214
pubmed: 23785486
pmcid: 3681972
Withers DJ, Gutierrez JS, Towery H, Burks DJ, Ren JM, Previs S, Zhang Y, Bernal D, Pons S, Shulman GI, Bonner-Weir S, White MF. Disruption of IRS-2 causes type 2 diabetes in mice. Nature. 1998;391:900–4. https://doi.org/10.1038/36116
pubmed: 9495343
Xia G, Zhu T, Li X, Jin Y, Zhou J, Xiao J. ROS-mediated autophagy through the AMPK signaling pathway protects INS-1 cells from human islet amyloid polypeptide-induced cytotoxicity. Mol Med Rep. 2018;18:2744–52. https://doi.org/10.3892/mmr.2018.9248 .
doi: 10.3892/mmr.2018.9248
pubmed: 30015901
pmcid: 6102651
Xu J, Lin S, Myers RW, Addona G, Berger JP, Campbell B, Chen H-S, Chen Z, Eiermann GJ, Elowe NH, Farrer BT, Feng W, Fu Q, Kats-Kagan R, Kavana M, Malkani S, McMasters DR, Mitra K, Pachanski MJ, Tong X, Trujillo ME, Xu L, Zhang B, Zhang F, Zhang R, Parmee ER. Novel, highly potent systemic glucokinase activators for the treatment of type 2 diabetes mellitus. Bioorg Med Chem Lett. 2017;27:2069–73. https://doi.org/10.1016/j.bmcl.2016.10.085
pubmed: 28284804
Yamaji T, Kumagai K, Tomishige N, Hanada K. Two sphingolipid transfer proteins, CERT and FAPP2: their roles in sphingolipid metabolism. IUBMB Life. 2008;60:511–8. https://doi.org/10.1002/iub.83
pubmed: 18459163
Yang Y-P, Thorel F, Boyer DF, Herrera PL, Wright CVE. Context-specific α- to-β-cell reprogramming by forced Pdx1 expression. Genes Dev. 2011;25:1680–5. https://doi.org/10.1101/gad.16875711
pubmed: 21852533
pmcid: 3165933
Yang S, Xia C, Li S, Du L, Zhang L, Zhou R. Defective mitophagy driven by dysregulation of rheb and KIF5B contributes to mitochondrial reactive oxygen species (ROS)-induced nod-like receptor 3 (NLRP3) dependent proinflammatory response and aggravates lipotoxicity. Redox Biol. 2014;3:63–71. https://doi.org/10.1016/j.redox.2014.04.001
pubmed: 25462067
pmcid: 4295565
Zhang S, Liu J, Dragunow M, Cooper GJS. Fibrillogenic amylin evokes islet beta-cell apoptosis through linked activation of a caspase cascade and JNK1. J Biol Chem. 2003;278:52810–9. https://doi.org/10.1074/jbc.M308244200
pubmed: 14532296
Zhang Y, Warnock GL, Ao Z, Park YJ, Safikhan N, Ghahary A, Marzban L. Amyloid formation reduces protein kinase B phosphorylation in primary islet β-cells which is improved by blocking IL-1β signaling. PLoS One. 2018;13:e0193184. https://doi.org/10.1371/journal.pone.0193184
pubmed: 29474443
pmcid: 5825069
Zhu Y, Liu Q, Zhou Z, Ikeda Y. PDX1, Neurogenin-3, and MAFA: critical transcription regulators for beta cell development and regeneration. Stem Cell Res Ther. 2017;8:240. https://doi.org/10.1186/s13287-017-0694-z
pubmed: 29096722
pmcid: 5667467
Zimmet P, Alberti KG, Shaw J. Global and societal implications of the diabetes epidemic. Nature. 2001;414:782–7. https://doi.org/10.1038/414782a
pubmed: 11742409
Zraika S, Hull RL, Verchere CB, Clark A, Potter KJ, Fraser PE, Raleigh DP, Kahn SE. Toxic oligomers and islet beta cell death: guilty by association or convicted by circumstantial evidence? Diabetologia. 2010;53:1046–56. https://doi.org/10.1007/s00125-010-1671-6
pubmed: 20182863
pmcid: 3164873