Pancreatic islet response to hyperglycemia is dependent on peroxisome proliferator-activated receptor alpha (PPARα)

This study tests the hypothesis that islet peroxisome proliferator-activated receptor alpha (PPAR alpha) influences insulin secretion. Freshly isolated islets of normoglycemic PPAR alpha-null mice display no major alteration of glucose-stimulated insulin release. However, after 24 h of culture in high glucose, PPAR alpha-null islets exhibit elevated basal insulin secretion and fail to increase insulin mRNA. 24-h culture with palmitate replicates this phenotype in wild-type islets. The data suggest that PPAR alpha is needed to ensure appropriate insulin secretory response in situation of short-term hyperglycemia, likely by maintaining islet lipid homeostasis. As such, islet PPAR alpha could contribute to delay the progression of type 2 diabetes. alpha 2005 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.