PPARβ/δ affects pancreatic β cell mass and insulin secretion in mice
José Iglesias, … , Bernard Thorens, Walter Wahli
José Iglesias, … , Bernard Thorens, Walter Wahli
Published October 24, 2012
Citation Information: J Clin Invest. 2012;122(11):4105-4117. https://doi.org/10.1172/JCI42127.
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Research Article Metabolism

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

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.

Authors

José Iglesias, Sebastian Barg, David Vallois, Shawon Lahiri, Catherine Roger, Akadiri Yessoufou, Sylvain Pradevand, Angela McDonald, Claire Bonal, Frank Reimann, Fiona Gribble, Marie-Bernard Debril, Daniel Metzger, Pierre Chambon, Pedro Herrera, Guy A. Rutter, Marc Prentki, Bernard Thorens, Walter Wahli

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