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

PPAR beta/delta 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 beta 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 beta cells indicated a broad repressive function of PPAR beta/delta affecting the vesicular and granular compartment as well as the actin cytoskeleton. Analyses of insulin release from isolated PPAR beta/delta-deficient islets revealed an accelerated second phase of glucose-stimulated insulin secretion. These effects in PPAR beta/delta-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 PPAR beta/delta in beta cell mass and insulin exocytosis, and shed a new light on PPAR beta/delta metabolic action.