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

Autor: Li-Xin Li, Frank Skorpen, Ingrid Hals Jørgensen, Kjartan Egeberg, Valdemar Grill
Rok vydání: 2002
Předmět:
Zdroj: Endocrinology. 143(4)
ISSN: 0013-7227
Popis: 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, P0.05 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, P0.05 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
Databáze: OpenAIRE