Title of article :
Uncoupling Protein-2 Negatively Regulates Insulin Secretion and Is a Major Link between Obesity, β Cell Dysfunction, and Type 2 Diabetes
Author/Authors :
Chenyu Zhang، نويسنده , , Gy?rgy Baffy، نويسنده , , Pascale Perret، نويسنده , , Stefan Krauss، نويسنده , , Odile Peroni، نويسنده , , Danica Grujic، نويسنده , , Thilo Hagen، نويسنده , , Antonio J. Vidal-Puig، نويسنده , , Olivier Boss، نويسنده , , Young-Bum Kim، نويسنده , , Xin Xiao Zheng، نويسنده , , Michael B. Wheeler، نويسنده , , Gerald I. Shulman، نويسنده , , Catherine B. Chan، نويسنده , , Bradford B. Lowell، نويسنده ,
Abstract :
β cells sense glucose through its metabolism and the resulting increase in ATP, which subsequently stimulates insulin secretion. Uncoupling protein-2 (UCP2) mediates mitochondrial proton leak, decreasing ATP production. In the present study, we assessed UCP2ʹs role in regulating insulin secretion. UCP2-deficient mice had higher islet ATP levels and increased glucose-stimulated insulin secretion, establishing that UCP2 negatively regulates insulin secretion. Of pathophysiologic significance, UCP2 was markedly upregulated in islets of ob/ob mice, a model of obesity-induced diabetes. Importantly, ob/ob mice lacking UCP2 had restored first-phase insulin secretion, increased serum insulin levels, and greatly decreased levels of glycemia. These results establish UCP2 as a key component of β cell glucose sensing, and as a critical link between obesity, β cell dysfunction, and type 2 diabetes.
