Effects of uncoupling protein-2 over-expression on the cyclic adenosine monophosphate signaling pathway of glucose-simulated insulin secretion

Insulin is a peptide hormone that promotes the removal of glucose from the blood and its storage or metabolism in muscle, liver and adipose cells. Obesity and type 2 diabetes mellitus are two of the largest health concerns facing society today and both metabolic disorders involve abnormalities in the relative level of insulin secretion from pancreatic β-cells. Elucidating the factors that control insulin secretion is vital to the development of effective therapies to counteract abnormal secretion. Uncoupling proteins (UCPs) uncouple electron transport from oxidative phosphorylation and attenuate the production ATP, a key messenger in the insulin secretory cascade. One member of the UCP family, UCP-2, is expressed in pancreatic islets and its overexpression leads to a decrease in both ATP production and glucose-stimulated insulin secretion (GSIS). While many ATP-dependent pathways exist which may be affected, the generation of cAMP and its ability to potentiate GSIS is the focus of this study. (Abstract shortened by UMI.).