Induction of uncoupling protein 2 mRNA in beta-cells is stimulated by oxidation of fatty acids but not by nutrient oversupply.

We tested for regulation of uncoupling protein 2 (UCP-2) in beta-cells in response to fatty acids and glucose. A 48-h culture with oleate (0.2 mM) at 5.5 or 11 mM glucose increased UCP-2 mRNA by 30-60% in INS-1 cells and in rat pancreatic islets. In contrast, oleate was ineffective after coculture at 27 mM glucose, P < 0.05 for difference 5.5 vs. 27 mM glucose. Also, culture with palmitate (0.1 mM) stimulated UCP-2 expression at 5.5 and 11 mM, but not at 27 mM glucose. Glucose per se failed to affect UCP-2 mRNA. Oxidation of [1-(14)C] oleate was increased by culture with oleate; however, this increase was attenuated by glucose during coculture, P < 0.05 for coculture at 5.5 vs. 27 mM glucose. Culture with aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside, an activator of AMP-activated protein kinase, decreased cellular triglycerides, increased postculture [1-(14)C] oleate oxidation, and increased UCP-2 mRNA. Etomoxir, an inhibitor of carnitine palmitoyltransferase I, decreased the oleate-induced increase in UCP-2 mRNA. Rosiglitazone, a peroxisome proliferator-activated receptor gamma ligand, affected neither UCP-2 mRNA nor [1-(14)C] oleate oxidation. Antioxidants (vitamin E and sodium selenite) did not affect oleate-induced UCP-2 mRNA. We conclude that: 1) UCP-2 mRNA is induced by fatty acid oxidation in beta-cells; and 2) glucose exerts a modulating effect that is coupled to inhibition of fatty acid oxidation