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PPARβ/δ affects pancreatic β cell mass and insulin secretion in mice

Iglesias, José
Barg, Sebastian
Vallois, David
Lahiri, Shawon
Roger, Catherine
Yessoufou, Akadiri
Pradevand, Sylvain
McDonald, Angela
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Published in Journal of Clinical Investigation. 2012, vol. 122, no. 11, p. 4105-17
Abstract PPARβ/δ protects against obesity by reducing dyslipidemia and insulin resistance via effects in muscle, adipose tissue, and liver. However, its function in pancreas remains ill defined. To gain insight into its hypothesized role in β cell function, we specifically deleted Pparb/d in the epithelial compartment of the mouse pancreas. Mutant animals presented increased numbers of islets and, more importantly, enhanced insulin secretion, causing hyperinsulinemia. Gene expression profiling of pancreatic β cells indicated a broad repressive function of PPARβ/δ affecting the vesicular and granular compartment as well as the actin cytoskeleton. Analyses of insulin release from isolated PPARβ/δ-deficient islets revealed an accelerated second phase of glucose-stimulated insulin secretion. These effects in PPARβ/δ-deficient islets correlated with increased filamentous actin (F-actin) disassembly and an elevation in protein kinase D activity that altered Golgi organization. Taken together, these results provide evidence for a repressive role for PPARβ/δ in β cell mass and insulin exocytosis, and shed a new light on PPARβ/δ metabolic action.
Keywords Actins/genetics/metabolismAnimalsExocytosis/physiologyFemaleGene Expression ProfilingGlucose/genetics/metabolismGolgi Apparatus/genetics/metabolismInsulin/genetics/secretionInsulin-Secreting Cells/cytology/secretionMaleMiceMice, Mutant StrainsPPAR delta/genetics/metabolismPPAR-beta/genetics/metabolismProtein Kinase C/genetics/metabolism
PMID: 23093780
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Research group Types cellulaires pancréatiques pendant l'ontogénèse (522)
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IGLESIAS, José et al. PPARβ/δ affects pancreatic β cell mass and insulin secretion in mice. In: Journal of Clinical Investigation, 2012, vol. 122, n° 11, p. 4105-17. https://archive-ouverte.unige.ch/unige:32137

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Deposited on : 2013-12-16

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