Upregulation of insulin receptor substrate-2 in pancreatic β cells prevents diabetes
Upregulation of insulin receptor substrate-2 in pancreatic β cells prevents diabetes
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DOI：
10.1172/jci200318581
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发表时间：
2003-11-01
影响因子：
15.9
通讯作者：
White, MF
中科院分区：
文献类型：
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作者：
Hennige, AM;Burks, DJ;White, MF
胰岛素/IGF信号系统的胰岛素受体底物-2 （Irs2）分支协调外周胰岛素作用和胰腺β细胞功能，因此缺乏Irs2的小鼠与2型糖尿病患者表现出相似之处。本研究表明，在Irs2（-/-）小鼠、肥胖小鼠和链脲佐菌素治疗小鼠中，低水平或高水平的β细胞特异性表达可产生分级生理反应，促进β细胞生长、存活和胰岛素分泌，从而预防糖尿病；移植后，转基因胰岛比WT型胰岛更有效地治愈糖尿病。因此，促进β细胞中Irs2表达的药理学方法，特别是特异性cAMP激动剂，可能是治疗β细胞衰竭和糖尿病的合理方法。
The insulin receptor substrate-2 (Irs2) branch of the insulin/IGF signaling system coordinates peripheral insulin action and pancreatic beta cell function, so mice lacking Irs2 display similarities to humans with type 2 diabetes. Here we show that beta cell-specific expression of Irs2 at a low or a high level delivered a graded physiologic response that promoted beta cell growth, survival, and insulin secretion that prevented diabetes in Irs2(-/-) mice, obese mice, and streptozotocin-treated mice; and that upon transplantation, the transgenic islets cured diabetes more effectively than WT islets. Thus, pharmacological approaches that promote Irs2 expression in beta cells, especially specific cAMP agonists, could be rational treatments for beta cell failure and diabetes.