Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Sci. STKE, 19 June 2001
Vol. 2001, Issue 87, p. tw5
[DOI: 10.1126/stke.2001.87.tw5]


Physiology UCP2, Insulin, and Type 2 Diabetes

Pancreatic beta cells release insulin in response to increased concentrations of serum glucose and its metabolites. Increasing concentrations of ATP (adenosine triphosphate), a product of glucose metabolism in mitochondria, cause beta cells to secrete insulin. Zhang et al. found that UCP2 (uncoupling protein-2), a protein that decreases the efficiency of ATP production in mitochondria by allowing protons to leak out through the mitochondrial membrane, negatively influences insulin secretion by controlling glucose-dependent ATP synthesis. Isolated pancreatic islet cells from ucp2-deficient mice produced larger amounts of ATP and secreted more insulin, and ucp2-deficient mice had lower serum concentrations of glucose. In hyperglycemic, insulin-resistant, obese (ob/ob) mice, amounts of both UCP2 protein and mRNA were greatly increased, suggesting that increased UCP2 might contribute to impaired beta cell function, leading to diabetes. Zhang et al. crossed ob/ob mice and ucp2-deficient mice and found that although the double-mutant mice were still obese, they were no longer hyperglycemic and secreted greater amounts of insulin compared with ob/ob mice, indicating that these double-mutant mice had improved beta cell function resulting from the absence of UCP2. Thus, these data indicate that UCP2 may link beta cell dysregulation to diabetes.

C.-Y. Zhang, G. Baffy, P. Perret, S. Krauss, O. Peroni, D. Grujic, T. Hagen, A. J. Vidal-Puig, O. Boss, Y.-B. Kim, X. X. Zheng, M. B. Wheeler, G. I. Shulman, C. B. Chan, B. B. Lowell, Uncoupling Protein-2 negatively regulates insulin secretion and is a major link between obesity, cell dysfunction, and type 2 diabetes. Cell 105, 745-755 (2001). [Online Journal]

Citation: UCP2, Insulin, and Type 2 Diabetes. Sci. STKE 2001, tw5 (2001).

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882