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
Li
Li-Xin
LX
Department of Medicine, Endocrine Section, Norwegian University of Science and Technology, N-7489 Trondheim, Norway.
Skorpen
Frank
F
Egeberg
Kjartan
K
Jørgensen
Ingrid Hals
IH
Grill
Valdemar
V
D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D003470:Culture Media; D004852:Epoxy Compounds / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007202:Indicators and Reagents; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007473:Ion Channels; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D026901:Membrane Transport Proteins; D008566:Membranes / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins; D010084:Oxidation-Reduction; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012265:Ribonucleotides / Q000494:pharmacology; D014280:Triglycerides / Q000378:metabolism; D000071246:Uncoupling Protein 2
D003470:Culture Media; D004852:Epoxy Compounds; D005227:Fatty Acids; D007004:Hypoglycemic Agents; D007202:Indicators and Reagents; D007328:Insulin; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D012265:Ribonucleotides; D014280:Triglycerides; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; D000620:Aminoimidazole Carboxamide; C031143:AICA ribonucleotide; D005947:Glucose; C054207:etomoxir