Regulation of insulin secretion in mouse islets: metabolic amplification by alpha-ketoisocaproate coincides with rapid and sustained increase in acetyl-CoA content.
Acetyl-CoA
Alpha-ketoisocaproate
Beta-cell
Glucose
Insulin secretion
Metabolic amplification
Journal
Naunyn-Schmiedeberg's archives of pharmacology
ISSN: 1432-1912
Titre abrégé: Naunyn Schmiedebergs Arch Pharmacol
Pays: Germany
ID NLM: 0326264
Informations de publication
Date de publication:
02 2023
02 2023
Historique:
received:
19
04
2022
accepted:
05
09
2022
pubmed:
11
11
2022
medline:
13
1
2023
entrez:
10
11
2022
Statut:
ppublish
Résumé
Glucose and alpha-ketoisocaproate, the keto acid analogue of leucine, stimulate insulin secretion in the absence of other exogenous fuels. Their mitochondrial metabolism in the beta-cell raises the cytosolic ATP/ADP ratio, thereby providing the triggering signal for the exocytosis of the insulin granules. However, additional amplifying signals are required for the full extent of insulin secretion stimulated by these fuels. While it is generally recognized that the amplifying signals are also derived from the mitochondrial metabolism, their exact nature is still unclear. The current study tests the hypothesis that the supply of cytosolic acetyl-CoA is a signal in the amplifying pathway. The contents of acetyl-CoA and acetyl-CoA plus CoA-SH were measured in isolated mouse islets. Insulin secretion was recorded in isolated perifused islets. In islets, the ATP-sensitive K
Identifiants
pubmed: 36355207
doi: 10.1007/s00210-022-02290-8
pii: 10.1007/s00210-022-02290-8
pmc: PMC9832085
doi:
Substances chimiques
alpha-ketoisocaproic acid
816-66-0
Acetyl Coenzyme A
72-89-9
Insulin
0
Adenosine Triphosphate
8L70Q75FXE
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
353-364Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : Ru 368/5-4
Informations de copyright
© 2022. The Author(s).
Références
Biochem J. 1980 Jan 15;186(1):135-44
pubmed: 6989358
Physiol Rev. 2018 Jan 1;98(1):117-214
pubmed: 29212789
Mol Pharmacol. 2005 Oct;68(4):1097-105
pubmed: 16014804
Diabetologia. 2005 Dec;48(12):2563-6
pubmed: 16283243
Endocrinology. 1980 Jan;106(1):203-19
pubmed: 6985583
Diabetes. 2000 Nov;49(11):1751-60
pubmed: 11078440
Metabolites. 2021 Jun 02;11(6):
pubmed: 34199454
Mol Pharmacol. 1981 Jul;20(1):76-82
pubmed: 6270540
Biochim Biophys Acta. 2013 Mar;1833(3):686-97
pubmed: 23247107
Diabetes. 1991 Mar;40(3):327-33
pubmed: 1999274
Metabolism. 2017 Feb;67:1-13
pubmed: 28081772
Nat Rev Mol Cell Biol. 2014 Aug;15(8):536-50
pubmed: 25053359
Cell Metab. 2013 Aug 6;18(2):162-85
pubmed: 23791483
Biochem J. 2006 Nov 15;400(1):81-9
pubmed: 16819942
Biochim Biophys Acta. 2006 Dec;1763(12):1697-706
pubmed: 17045662
J Biol Chem. 2010 Oct 29;285(44):33718-26
pubmed: 20736162
Diabetologia. 2020 Jan;63(1):10-20
pubmed: 31423551
Cell Death Dis. 2019 Jan 25;10(2):66
pubmed: 30683850
Am J Physiol Endocrinol Metab. 2008 Dec;295(6):E1287-97
pubmed: 18728221
Diabetologia. 2019 Jan;62(1):99-111
pubmed: 30334081
J Biol Chem. 1980 Jan 25;255(2):413-8
pubmed: 7356624
Am J Physiol Endocrinol Metab. 2005 Jan;288(1):E1-15
pubmed: 15585595
J Biol Chem. 2013 Apr 12;288(15):10923-35
pubmed: 23426361
Biochem J. 2009 Apr 15;419(2):359-68
pubmed: 19173679
J Biol Chem. 2014 May 2;289(18):12189-94
pubmed: 24637025
Chembiochem. 2011 Jan 24;12(2):290-8
pubmed: 21243716
Diabetologia. 1973 Apr;9(2):115-9
pubmed: 4577291
Metabolism. 2013 Oct;62(10):1375-86
pubmed: 23790612
Biochem J. 1993 Oct 1;295 ( Pt 1):31-40
pubmed: 8216234
Diabetologia. 2010 Jun;53(6):1019-32
pubmed: 20225132
Diabetologia. 2009 May;52(5):739-51
pubmed: 19288076
Metabolism. 2016 Sep;65(9):1225-9
pubmed: 27506729
Nat Rev Mol Cell Biol. 2021 Feb;22(2):142-158
pubmed: 33398164
Anal Biochem. 1975 Jun;66(2):372-92
pubmed: 1137102
Diabetologia. 2008 Jan;51(1):101-9
pubmed: 17960358
Biochim Biophys Acta. 2016 Oct;1864(10):1372-401
pubmed: 27296530
J Clin Invest. 2007 Sep;117(9):2539-52
pubmed: 17694178
Am J Physiol Endocrinol Metab. 2002 Aug;283(2):E302-10
pubmed: 12110535
J Endocrinol. 2015 Jan;224(1):75-84
pubmed: 25453115
Methods Mol Biol. 2012;933:189-201
pubmed: 22893408
Diabetes. 2018 Mar;67(3):496-506
pubmed: 29229615