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Induction of Uncoupling Protein 2 mRNA in ß-Cells Is Stimulated by Oxidation of Fatty Acids But Not by Nutrient Oversupply

Department of Medicine (L.-X.L., I.H.J., V.G.), Endocrine Section, Institute of Cancer Research and Molecular Biology (F.S., K.E.), Medical Faculty, Norwegian University of Science and Technology, N-7489 Trondheim, Norway

Address all correspondence and requests for reprints to: Valdemar Grill, M.D., Ph.D., Endocrine Section, Medical Faculty, Norwegian University of Science and Technology, N-7489 Trondheim, Norway. E-mail: . valdemar.grill{at}medisin.ntnu.no

We tested for regulation of uncoupling protein 2 (UCP-2) in ß-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 [1-¹⁴C] 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-ß-D-ribofuranoside, an activator of AMP-activated protein kinase, decreased cellular triglycerides, increased postculture [1-¹⁴C] 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 ligand, affected neither UCP-2 mRNA nor [1-¹⁴C] 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 ß-cells; and 2) glucose exerts a modulating effect that is coupled to inhibition of fatty acid oxidation

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