Diverse roles for protein kinase C delta and protein kinase C epsilon in the generation of high-fat-diet-induced glucose intolerance in mice: regulation of lipogenesis by protein kinase C delta
- PMID: 19809797
- DOI: 10.1007/s00125-009-1543-0
Diverse roles for protein kinase C delta and protein kinase C epsilon in the generation of high-fat-diet-induced glucose intolerance in mice: regulation of lipogenesis by protein kinase C delta
Abstract
Aims/hypothesis: This study aimed to determine whether protein kinase C (PKC) delta plays a role in the glucose intolerance caused by a high-fat diet, and whether it could compensate for loss of PKCepsilon in the generation of insulin resistance in skeletal muscle.
Methods: Prkcd (-/-), Prkce (-/-) and wild-type mice were fed high-fat diets and subjected to glucose tolerance tests. Blood glucose levels and insulin responses were determined during the tests. Insulin signalling in liver and muscle was assessed after acute in vivo insulin stimulation by immunoblotting with phospho-specific antibodies. Activation of PKC isoforms in muscle from Prkce (-/-) mice was assessed by determining intracellular distribution. Tissues and plasma were assayed for triacylglycerol accumulation, and hepatic production of lipogenic enzymes was determined by immunoblotting.
Results: Both Prkcd (-/-) and Prkce (-/-) mice were protected against high-fat-diet-induced glucose intolerance. In Prkce (-/-) mice this was mediated through enhanced insulin availability, while in Prkcd (-/-) mice the reversal occurred in the absence of elevated insulin. Neither the high-fat diet nor Prkcd deletion affected maximal insulin signalling. The activation of PKCdelta in muscle from fat-fed mice was enhanced by Prkce deletion. PKCdelta-deficient mice exhibited reduced liver triacylglycerol accumulation and diminished production of lipogenic enzymes.
Conclusions/interpretation: Deletion of genes encoding isoforms of PKC can improve glucose intolerance, either by enhancing insulin availability in the case of Prkce, or by reducing lipid accumulation in the case of Prkcd. The absence of PKCepsilon in muscle may be compensated by increased activation of PKCdelta in fat-fed mice, suggesting that an additional role for PKCepsilon in this tissue is masked.
Similar articles
-
Time-dependent effects of Prkce deletion on glucose homeostasis and hepatic lipid metabolism on dietary lipid oversupply in mice.Diabetologia. 2011 Jun;54(6):1447-56. doi: 10.1007/s00125-011-2073-0. Epub 2011 Feb 24. Diabetologia. 2011. PMID: 21347625
-
Proteomic analysis of livers from fat-fed mice deficient in either PKCδ or PKCε identifies Htatip2 as a regulator of lipid metabolism.Proteomics. 2014 Nov;14(21-22):2578-87. doi: 10.1002/pmic.201400202. Epub 2014 Oct 14. Proteomics. 2014. PMID: 25175814
-
PKCδ regulates hepatic insulin sensitivity and hepatosteatosis in mice and humans.J Clin Invest. 2011 Jun;121(6):2504-17. doi: 10.1172/JCI46045. Epub 2011 May 16. J Clin Invest. 2011. PMID: 21576825 Free PMC article.
-
Protein Kinase C δ: a Gatekeeper of Immune Homeostasis.J Clin Immunol. 2016 Oct;36(7):631-40. doi: 10.1007/s10875-016-0323-0. Epub 2016 Aug 19. J Clin Immunol. 2016. PMID: 27541826 Free PMC article. Review.
-
Phenotypic Variability in PRKCD: a Review of the Literature.J Clin Immunol. 2023 Nov;43(8):1692-1705. doi: 10.1007/s10875-023-01579-4. Epub 2023 Oct 5. J Clin Immunol. 2023. PMID: 37794137 Review.
Cited by
-
Epoxygenase Cyp2c44 Regulates Hepatic Lipid Metabolism and Insulin Signaling by Controlling FATP2 Localization and Activation of the DAG/PKCδ Axis.Diabetes. 2024 Aug 1;73(8):1229-1243. doi: 10.2337/db23-0493. Diabetes. 2024. PMID: 38743615
-
Revealing myopathy spectrum: integrating transcriptional and clinical features of human skeletal muscles with varying health conditions.Commun Biol. 2024 Apr 10;7(1):438. doi: 10.1038/s42003-024-06143-3. Commun Biol. 2024. PMID: 38600180 Free PMC article.
-
Rottlerin suppresses lipid accumulation by inhibiting de novo lipogenesis and adipogenesis via LRP6/mTOR/SREBP1C in 3T3-L1 adipocytes.Food Sci Biotechnol. 2023 Jun 30;32(10):1445-1452. doi: 10.1007/s10068-023-01339-5. eCollection 2023 Sep. Food Sci Biotechnol. 2023. PMID: 37457404 Free PMC article.
-
Platelet-Activating Factor Promotes the Development of Non-Alcoholic Fatty Liver Disease.Diabetes Metab Syndr Obes. 2022 Jul 8;15:2003-2030. doi: 10.2147/DMSO.S367483. eCollection 2022. Diabetes Metab Syndr Obes. 2022. PMID: 35837578 Free PMC article. Review.
-
LPIN1 Induces Gefitinib Resistance in EGFR Inhibitor-Resistant Non-Small Cell Lung Cancer Cells.Cancers (Basel). 2022 Apr 29;14(9):2222. doi: 10.3390/cancers14092222. Cancers (Basel). 2022. PMID: 35565351 Free PMC article.
References
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Miscellaneous