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

Endocrinology. 2002 Apr;143(4):1371-7. doi: 10.1210/endo.143.4.8717.

Abstract

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoimidazole Carboxamide / analogs & derivatives*
  • Aminoimidazole Carboxamide / pharmacology
  • Animals
  • Blotting, Western
  • Cells, Cultured
  • Culture Media
  • Epoxy Compounds / pharmacology
  • Fatty Acids / metabolism*
  • Glucose / pharmacology
  • Hypoglycemic Agents / pharmacology
  • Indicators and Reagents
  • Insulin / metabolism
  • Insulin Secretion
  • Ion Channels
  • Islets of Langerhans / metabolism*
  • Male
  • Membrane Potentials / physiology
  • Membrane Transport Proteins*
  • Membranes / metabolism
  • Mitochondria / metabolism
  • Mitochondrial Proteins*
  • Oxidation-Reduction
  • Protein Biosynthesis*
  • RNA, Messenger / biosynthesis*
  • Rats
  • Rats, Sprague-Dawley
  • Ribonucleotides / pharmacology
  • Triglycerides / metabolism
  • Uncoupling Protein 2

Substances

  • Culture Media
  • Epoxy Compounds
  • Fatty Acids
  • Hypoglycemic Agents
  • Indicators and Reagents
  • Insulin
  • Ion Channels
  • Membrane Transport Proteins
  • Mitochondrial Proteins
  • RNA, Messenger
  • Ribonucleotides
  • Triglycerides
  • Ucp2 protein, rat
  • Uncoupling Protein 2
  • Aminoimidazole Carboxamide
  • AICA ribonucleotide
  • Glucose
  • etomoxir