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 (PPARα) influences insulin secretion. Freshly isolated islets of normoglycemic PPARα-null mice display no major alteration of glucose-stimulated insulin release. However, after 24 h of culture in high glucose, PPARα-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 PPARα is needed to ensure appropriate insulin secretory response in situation of short-term hyperglycemia, likely by maintaining islet lipid homeostasis. As such, islet PPARα could contribute to delay the progression of type 2 diabetes.