title: 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.affiliation: Center for Integrative Genomics, National Research Center Frontiers in Genetics, University of Lausanne, Lausanne, Switzerland.
authors.forename: José
authors.initials: J
authors.lastname: Iglesias
authors.forename: Sebastian
authors.initials: S
authors.lastname: Barg
authors.forename: David
authors.initials: D
authors.lastname: Vallois
authors.forename: Shawon
authors.initials: S
authors.lastname: Lahiri
authors.forename: Catherine
authors.initials: C
authors.lastname: Roger
authors.forename: Akadiri
authors.initials: A
authors.lastname: Yessoufou
authors.forename: Sylvain
authors.initials: S
authors.lastname: Pradevand
authors.forename: Angela
authors.initials: A
authors.lastname: McDonald
authors.forename: Claire
authors.initials: C
authors.lastname: Bonal
authors.forename: Frank
authors.initials: F
authors.lastname: Reimann
authors.forename: Fiona
authors.initials: F
authors.lastname: Gribble
authors.forename: Marie-Bernard
authors.initials: MB
authors.lastname: Debril
authors.forename: Daniel
authors.initials: D
authors.lastname: Metzger
authors.forename: Pierre
authors.initials: P
authors.lastname: Chambon
authors.forename: Pedro
authors.initials: P
authors.lastname: Herrera
authors.forename: Guy A
authors.initials: GA
authors.lastname: Rutter
authors.forename: Marc
authors.initials: M
authors.lastname: Prentki
authors.forename: Bernard
authors.initials: B
authors.lastname: Thorens
authors.forename: Walter
authors.initials: W
authors.lastname: Wahli
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D005089:Exocytosis / Q000502:physiology; D005260:Female; D020869:Gene Expression Profiling; D005947:Glucose / Q000235:genetics / Q000378:metabolism; D006056:Golgi Apparatus / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D047494:PPAR delta / Q000235:genetics / Q000378:metabolism*; D048068:PPAR-beta / Q000235:genetics / Q000378:metabolism*; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D007328:Insulin; D047494:PPAR delta; D048068:PPAR-beta; C089212:protein kinase D; D011493:Protein Kinase C; D005947:Glucose