Uncoupling Protein 2: A Possible Link Between Fatty Acid Excess and Impaired Glucose-Induced Insulin Secretion?
- 1 April 2001
- journal article
- Published by American Diabetes Association in Diabetes
- Vol. 50 (4) , 803-809
- https://doi.org/10.2337/diabetes.50.4.803
Abstract
The mechanism by which long-term exposure of the β-cell to elevated concentrations of fatty acid alters glucose-induced insulin secretion has been examined. Exposure of INS-1 β-cells to 0.4 mmol/l oleate for 72 h increased basal insulin secretion and decreased insulin release in response to high glucose, but not in response to agents acting at the level of the KATP channel (tolbutamide) or beyond (elevated KCl). This also suppressed the glucose-induced increase in the cellular ATP-to-ADP ratio. The depolarization of the plasma membrane promoted by glucose was decreased after oleate exposure, whereas the response to KCl was unchanged. Cells exposed to free fatty acids displayed a lower mitochondrial membrane potential and a decreased glucose-induced hyperpolarization. The possible implication of uncoupling protein (UCP)-2 in the altered secretory response was examined by measuring UCP2 gene expression after chronic exposure of the cells to fatty acids. UCP2 mRNA and protein were increased twofold by oleate. Palmitate and the nonoxidizable fatty acid bromopalmitate had similar effects on UCP2 mRNA, suggesting that UCP2 gene induction by fatty acids does not require their metabolism. The data are compatible with a role of UCP2 and partial mitochondrial uncoupling in the decreased secretory response to glucose observed after chronic exposure of the β-cell to elevated fatty acids, and suggest that the expression and/or activity of the protein may modulate insulin secretion in response to glucose.Keywords
This publication has 53 references indexed in Scilit:
- Sodium Palmitate Induces Partial Mitochondrial Uncoupling and Reactive Oxygen Species in Rat Pancreatic Islets in VitroEndocrinology, 1999
- Increase in Uncoupling Protein-2 mRNA Expression by BRL49653 and Bromopalmitate in Human AdipocytesBiochemical and Biophysical Research Communications, 1999
- Peroxisome Proliferator-Activated Receptors and Mediate in Vivo Regulation of Uncoupling Protein (UCP-1, UCP-2, UCP-3) Gene ExpressionEndocrinology, 1998
- Thiazolidinediones Stimulate Uncoupling Protein-2 Expression in Cell Lines Representing White and Brown Adipose Tissues and Skeletal MuscleEndocrinology, 1998
- Induction of Uncoupling Protein-2 mRNA by Troglitazone in the Pancreatic Islets of Zucker Diabetic Fatty RatsBiochemical and Biophysical Research Communications, 1997
- Fatty Acids Rapidly Induce the Carnitine Palmitoyltransferase I Gene in the Pancreatic β-Cell Line INS-1Published by Elsevier ,1997
- Activation of the ATP-sensitive K+ Channel by Long Chain Acyl-CoAPublished by Elsevier ,1996
- Long-term exposure of rat pancreatic islets to fatty acids inhibits glucose-induced insulin secretion and biosynthesis through a glucose fatty acid cycle.Journal of Clinical Investigation, 1994
- Influence of fatty acids on energy metabolismEuropean Journal of Biochemistry, 1984
- THE GLUCOSE FATTY-ACID CYCLE ITS ROLE IN INSULIN SENSITIVITY AND THE METABOLIC DISTURBANCES OF DIABETES MELLITUSPublished by Elsevier ,1963