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Title

Regulation of PKD by the MAPK p38delta in insulin secretion and glucose homeostasis

Authors
Sumara, Grzegorz
Formentini, Ivan
Collins, Stephan
Sumara, Izabela
Windak, Renata
Bodenmiller, Bernd
Ramracheya, Reshma
Caille, Dorothee
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Published in Cell. 2009, vol. 136, no. 2, p. 235-248
Abstract Dysfunction and loss of insulin-producing pancreatic beta cells represent hallmarks of diabetes mellitus. Here, we show that mice lacking the mitogen-activated protein kinase (MAPK) p38delta display improved glucose tolerance due to enhanced insulin secretion from pancreatic beta cells. Deletion of p38delta results in pronounced activation of protein kinase D (PKD), the latter of which we have identified as a pivotal regulator of stimulated insulin exocytosis. p38delta catalyzes an inhibitory phosphorylation of PKD1, thereby attenuating stimulated insulin secretion. In addition, p38delta null mice are protected against high-fat-feeding-induced insulin resistance and oxidative stress-mediated beta cell failure. Inhibition of PKD1 reverses enhanced insulin secretion from p38delta-deficient islets and glucose tolerance in p38delta null mice as well as their susceptibility to oxidative stress. In conclusion, the p38delta-PKD pathway integrates regulation of the insulin secretory capacity and survival of pancreatic beta cells, pointing to a pivotal role for this pathway in the development of overt diabetes mellitus.
Keywords AnimalsExocytosisFemaleGlucose/metabolismGolgi Apparatus/metabolismInsulin/*secretionInsulin-Secreting Cells/*metabolismMaleMiceMitogen-Activated Protein Kinase 13/genetics/*metabolismProtein Kinase C/*metabolismType C Phospholipases/metabolism
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PMID: 19135240
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Research group Couplage cellulaire et connexines (136)
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SUMARA, Grzegorz et al. Regulation of PKD by the MAPK p38delta in insulin secretion and glucose homeostasis. In: Cell, 2009, vol. 136, n° 2, p. 235-248. doi: 10.1016/j.cell.2008.11.018 https://archive-ouverte.unige.ch/unige:20119

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Deposited on : 2012-04-23

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