A protein kinase C α and β inhibitor blunts hyperphagia to halt renal function decline and reduces adiposity in a rat model of obesity-driven type 2 diabetes.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
07 10 2023
07 10 2023
Historique:
received:
28
12
2022
accepted:
28
09
2023
medline:
1
11
2023
pubmed:
8
10
2023
entrez:
7
10
2023
Statut:
epublish
Résumé
Type 2 diabetes (T2D) and its complications can have debilitating, sometimes fatal consequences for afflicted individuals. The disease can be difficult to control, and therapeutic strategies to prevent T2D-induced tissue and organ damage are needed. Here we describe the results of administering a potent and selective inhibitor of Protein Kinase C (PKC) family members PKCα and PKCβ, Cmpd 1, in the ZSF1 obese rat model of hyperphagia-induced, obesity-driven T2D. Although our initial intent was to evaluate the effect of PKCα/β inhibition on renal damage in this model setting, Cmpd 1 unexpectedly caused a marked reduction in the hyperphagic response of ZSF1 obese animals. This halted renal function decline but did so indirectly and indistinguishably from a pair feeding comparator group. However, above and beyond this food intake effect, Cmpd 1 lowered overall animal body weights, reduced liver vacuolation, and reduced inguinal adipose tissue (iWAT) mass, inflammation, and adipocyte size. Taken together, Cmpd 1 had strong effects on multiple disease parameters in this obesity-driven rodent model of T2D. Further evaluation for potential translation of PKCα/β inhibition to T2D and obesity in humans is warranted.
Identifiants
pubmed: 37805649
doi: 10.1038/s41598-023-43759-7
pii: 10.1038/s41598-023-43759-7
pmc: PMC10560236
doi:
Substances chimiques
Protein Kinase C-alpha
EC 2.7.11.13
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
16919Informations de copyright
© 2023. Springer Nature Limited.
Références
PLoS One. 2017 Jan 25;12(1):e0170219
pubmed: 28121997
Am J Physiol. 1982 Jun;242(6):E353-9
pubmed: 6953766
Diabetes Care. 2013 Apr;36(4):1033-46
pubmed: 23468086
Biochem J. 2016 Dec 15;473(24):4681-4697
pubmed: 27784766
Diabetes Care. 2007 Apr;30(4):995-6
pubmed: 17229944
Diabetes Care. 2006 Apr;29(4):864-8
pubmed: 16567829
PLoS One. 2017 Jul 26;12(7):e0181861
pubmed: 28746409
J Am Soc Nephrol. 2003 Aug;14(8 Suppl 3):S227-32
pubmed: 12874436
Diabetes. 2003 Feb;52(2):512-8
pubmed: 12540629
Science. 2002 Dec 6;298(5600):1912-34
pubmed: 12471243
J Biol Chem. 2011 Jul 1;286(26):22795-805
pubmed: 21550971
J Am Soc Nephrol. 2003 Aug;14(8):2015-24
pubmed: 12874455
Pharmacoeconomics. 2015 Aug;33(8):811-31
pubmed: 25787932
Kidney Int. 2004 Sep;66(3):1107-14
pubmed: 15327405
Front Neurosci. 2018 Dec 11;12:930
pubmed: 30618559
Diabetes. 2008 Mar;57(3):706-13
pubmed: 18086904
Diabetes. 2004 Aug;53(8):2101-9
pubmed: 15277392
Diabetes. 2013 Apr;62(4):1167-74
pubmed: 23434935
J Am Soc Nephrol. 2007 Nov;18(11):2945-52
pubmed: 17928507
J Biol Chem. 2008 Aug 22;283(34):23033-8
pubmed: 18562307
Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):11059-63
pubmed: 1438315
Proc Natl Acad Sci U S A. 1989 Jul;86(13):5141-5
pubmed: 2740348
Neuropsychopharmacology. 2017 Jun;42(7):1491-1501
pubmed: 28128334
J Am Soc Nephrol. 1996 Jan;7(1):113-7
pubmed: 8808117
Diabetes. 2015 Mar;64(3):867-75
pubmed: 25294945
Nature. 2004 Apr 1;428(6982):569-74
pubmed: 15058305
Nature. 2002 Jan 17;415(6869):339-43
pubmed: 11797013
Diabetes Care. 2005 Nov;28(11):2686-90
pubmed: 16249540
Trends Pharmacol Sci. 2010 Jan;31(1):8-14
pubmed: 19969380
J Clin Invest. 1989 May;83(5):1667-75
pubmed: 2708528
J Diabetes Res. 2015;2015:801348
pubmed: 25945357
J Biol Chem. 2004 Oct 29;279(44):45304-7
pubmed: 15364919
Am J Physiol Renal Physiol. 2007 Nov;293(5):F1605-13
pubmed: 17728379
Clin J Am Soc Nephrol. 2007 Jul;2(4):631-6
pubmed: 17699475
J Lab Clin Med. 1981 Jul;98(1):46-57
pubmed: 7252327
Kidney Int. 2006 Oct;70(8):1456-62
pubmed: 16955103
Circ Res. 2010 Oct 29;107(9):1058-70
pubmed: 21030723
Nat Cell Biol. 2002 Jun;4(6):399-407
pubmed: 12032545
Diabetes Care. 2013 Apr;36(4):775-6
pubmed: 23520368
Diabetes. 2006 Nov;55(11):3112-20
pubmed: 17065350
ScientificWorldJournal. 2008 Aug 31;8:835-44
pubmed: 18758661
Hepatology. 2009 May;49(5):1525-36
pubmed: 19296465
Diabetes. 2007 Feb;56(2):346-54
pubmed: 17259378
Drug Metab Dispos. 2006 Nov;34(11):1909-17
pubmed: 16896067
PLoS One. 2010 Apr 16;5(4):e10185
pubmed: 20419132
Diabetologia. 2008 Apr;51(4):668-74
pubmed: 18278479
Rev Esp Enferm Dig. 2017 Jul;109(7):491-497
pubmed: 28593786
Int J Endocrinol. 2014;2014:968681
pubmed: 24648839
J Am Soc Nephrol. 2009 Apr;20(4):798-806
pubmed: 19279126
Diabetes Res Clin Pract. 1999 Sep;45(2-3):147-51
pubmed: 10588367
Diabetes. 2013 Apr;62(4):1010-1
pubmed: 23520273
FASEB J. 2000 Mar;14(3):439-47
pubmed: 10698958
Clin Pharmacokinet. 2006;45(3):297-303
pubmed: 16509761
J Clin Invest. 1997 Jul 1;100(1):115-26
pubmed: 9202063
Nephron. 1978;22(4-6):454-9
pubmed: 105300
J Endocrinol. 2011 Sep;210(3):293-308
pubmed: 21680617
Recent Prog Horm Res. 2001;56:309-28
pubmed: 11237219
J Am Soc Nephrol. 2007 Apr;18(4):1190-8
pubmed: 17360953
Circ Heart Fail. 2009 Mar;2(2):129-37
pubmed: 19808328
Ren Fail. 2000;22(4):387-406
pubmed: 10901178
Am J Physiol Gastrointest Liver Physiol. 2017 Mar 1;312(3):G266-G273
pubmed: 28104587
Science. 1996 May 3;272(5262):728-31
pubmed: 8614835
Semin Nephrol. 2007 Mar;27(2):195-207
pubmed: 17418688
J Lipid Res. 2012 Mar;53(3):368-378
pubmed: 22210924
Drug Metab Dispos. 2006 Feb;34(2):213-24
pubmed: 16258078
Physiol Rev. 2013 Jan;93(1):137-88
pubmed: 23303908