Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene
Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene
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DOI：
10.1126/science.283.5407.1544
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发表时间：
1999-03-05
期刊：
影响因子：
56.9
通讯作者：
Kennedy, BP
中科院分区：
文献类型：
--
作者：
Elchebly, M;Payette, P;Kennedy, BP
蛋白酪氨酸磷酸酶-1B（PTP-1B）参与胰岛素信号的负调节。破坏编码PTP-1B的基因的小鼠同源物产生了健康的小鼠，在进食状态下，血糖浓度略低，循环胰岛素浓度是PIP-1B（+/+）同窝仔的一半。PTP-1B（-/-）小鼠的胰岛素敏感性增强在葡萄糖和胰岛素耐量试验中也是明显的。与PTP-1B（+/+）小鼠相比，PTP-1B（-/-）小鼠在胰岛素注射后显示肝脏和肌肉组织中胰岛素受体的磷酸化增加。在高脂肪饮食中，PTP-1B（-/-）和PTP-1B（+/-）小鼠对体重增加有抵抗力，并保持胰岛素敏感性，而PTP-1B（+/+）小鼠体重迅速增加，并出现胰岛素抵抗。这些结果表明，PTP-1B在调节胰岛素敏感性和燃料代谢方面具有重要作用，从而将其确立为治疗2型糖尿病和肥胖症的潜在治疗靶点。
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 PIP-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.