| First Author | Joseph JW | Year | 2002 |
| Journal | Diabetes | Volume | 51 |
| Issue | 11 | Pages | 3211-9 |
| PubMed ID | 12401712 | Mgi Jnum | J:107179 |
| Mgi Id | MGI:3620381 | Doi | 10.2337/diabetes.51.11.3211 |
| Citation | Joseph JW, et al. (2002) Uncoupling protein 2 knockout mice have enhanced insulin secretory capacity after a high-fat diet. Diabetes 51(11):3211-9 |
| abstractText | Uncoupling protein 2 (UCP2) may act as an important regulator of insulin secretion. In this study, beta-cell function in UCP2-deficient mice was examined after a 45% high-fat diet (HFD) to assess its role during the development of diet-induced type 2 diabetes. HFD-fed UCP2 (-/-) mice have lower fasting blood glucose and elevated insulin levels when compared with wild-type (WT) mice. UCP2 (-/-) mice also have enhanced beta-cell glucose sensitivity compared with WT mice after HFD, a result that is due in part to the deterioration of glucose responsiveness in WT mice. HFD-fed UCP2 (-/-) mice have increased insulin secretory capacity as a result of increased pancreatic beta-cell mass and insulin content per islet. Islets from WT mice exposed to 0.5 mmol/l palmitate for 48 h have significantly reduced mitochondrial membrane potential, ATP concentrations, and glucose responsiveness compared with UCP2 (-/-) islets, suggesting that elevated UCP2 in WT mice increases proton leak and decreases mitochondrial ATP production. Highly increased carnitine palmitoyl transferase-1 gene expression in UCP2 (-/-) mice is suggestive of enhanced fatty acid oxidizing capacity, particularly after HFD stress. These results further establish UCP2 as a component in glucose sensing and suggest a possible new aspect of UCP2 function during the progression of type 2 diabetes. |
