Increased Insulin Sensitivity and Obesity Resistance in Mice Lacking the Protein Tyrosine Phosphatase-1B Gene

作者：Mounib Elchebly, Paul Payette, Eva Michaliszyn, Wanda A. Cromlish, Susan Collins, Ailsa Lee Loy, Denis Normandin, Alan C. Cheng, Jean Himms‐Hagen, Chi‐Chung Chan, Chidambaram Ramachandran, Michael J. Gresser, Michel L. Tremblay, Brian Patrick Kennedy · 发表于：Science · 年份：1999 · DOI：10.1126/science.283.5407.1544 · 被引用次数：2219 · 研究领域：Protein Tyrosine Phosphatases、Diet, Metabolism, and Disease、Metabolism, Diabetes, and Cancer

Protein tyrosine phosphatase-1B (PTP-1B) has been implicated in the negative regulation of insulin signaling. Disruption of the mouse homolog of the gene encoding PTP-1B yielded healthy mice that, in the fed state, had blood glucose concentrations that were slightly lower and concentrations of circulating insulin that were one-half those of their PTP-1B+/+ littermates. The enhanced insulin sensitivity of the PTP-1B-/- mice was also evident in glucose and insulin tolerance tests. The PTP-1B-/- mice showed increased phosphorylation of the insulin receptor in liver and muscle tissue after insulin injection in comparison to PTP-1B+/+ mice. On a high-fat diet, the PTP-1B-/- and PTP-1B+/- mice were resistant to weight gain and remained insulin sensitive, whereas the PTP-1B+/+ mice rapidly gained weight and became insulin resistant. These results demonstrate that PTP-1B has a major role in modulating both insulin sensitivity and fuel metabolism, thereby establishing it as a potential therapeutic target in the treatment of type 2 diabetes and obesity.