The pancreatic β cell is a key site for mediating the effects of leptin on glucose homeostasis
The pancreatic β cell is a key site for mediating the effects of leptin on glucose homeostasis
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DOI：
10.1016/j.cmet.2006.09.005
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发表时间：
2006-10-01
期刊：
影响因子：
29
通讯作者：
Kieffer, Timothy J.
中科院分区：
文献类型：
--
作者：
Covey, Scott D.;Wideman, Rhonda D.;Kieffer, Timothy J.
瘦素激素在维持体重和血糖动态平衡方面起着至关重要的作用。这是通过中枢和外周途径发生的，包括调节胰岛β细胞的胰岛素分泌。为了在小鼠身上进一步研究这一点，我们破坏了β细胞和下丘脑中瘦素受体基因的信号域。这些小鼠出现肥胖、空腹高胰岛素血症、葡萄糖刺激的胰岛素释放受损和葡萄糖耐量异常，类似于瘦素受体缺失的小鼠。然而，尽管瘦素功能的完全丧失会导致食物摄入量增加，但这种组织特异性的瘦素信号减弱并不会改变食物摄入量或对瘦素的饱腹感反应。此外，与其他肥胖模型不同，这些小鼠降低了空腹血糖。这些结果表明，瘦素对葡萄糖稳态的调节超越了胰岛素敏感性，影响了胰岛细胞的功能，而不依赖于控制食物摄入量的途径。这些数据表明，该节点轴的缺陷可能导致与肥胖相关的糖尿病。
The hormone leptin plays a crucial role in maintenance of body weight and glucose homeostasis. This occurs through central and peripheral pathways, including regulation of insulin secretion by pancreatic beta cells. To study this further in mice, we disrupted the signaling domain of the leptin receptor gene in beta cells and hypothalamus. These mice develop obesity, fasting hyperinsulinemia, impaired glucose-stimulated insulin release, and glucose intolerance, similar to leptin receptor null mice. However, whereas complete loss of leptin function causes increased food intake, this tissue-specific attenuation of leptin signaling does not alter food intake or satiety responses to leptin. Moreover, unlike other obese models, these mice have reduced fasting blood glucose. These results indicate that leptin regulation of glucose homeostasis extends beyond insulin sensitivity to influence beta cell function, independent of pathways controlling food intake. These data suggest that defects in this adipoinsular axis could contribute to diabetes associated with obesity.