Lilly Lecture, 2003 - The struggle for mastery in insulin action: From triumvirate to republic
Lilly Lecture, 2003 - The struggle for mastery in insulin action: From triumvirate to republic
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DOI：
10.2337/diabetes.53.7.1633
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发表时间：
2004-07-01
期刊：
影响因子：
7.7
通讯作者：
Accili, D
中科院分区：
文献类型：
--
作者：
Accili, D
2型糖尿病是由胰岛素作用受损和胰腺β细胞功能缺陷的组合引起的。传统上，这两种异常被视为不同但相互有害的过程。骨骼肌中胰岛素依赖性葡萄糖代谢受损和β细胞功能受损的组合导致肝脏葡萄糖产生增加，导致一系列组织异常，被称为糖尿病的“统治三巨头”。“小鼠的靶向诱变导致了对胰岛素作用的综合生理学的重要重新评估。这些研究表明，骨骼肌和脂肪组织中的胰岛素抵抗并不一定导致高血糖症，只要其他组织中的胰岛素敏感性保持不变。其他数据表明胰岛素信号在β细胞功能和β细胞质量调节中发挥直接作用，从而提高了胰岛素抵抗可能是所有靶组织中糖尿病的首要特征的可能性。我建议我们把原来的三巨头统治的画面换成一个争吵不休的共和国，在这个共和国中，每一个组织都有助于疾病的发生。
Type 2 diabetes arises from a combination of impaired insulin action and defective pancreatic beta-cell function. Classically, the two abnormalities have been viewed as distinct yet mutually detrimental processes. The combination of impaired insulin-dependent glucose metabolism in skeletal muscle and impaired beta-cell function causes an increase of hepatic glucose production, leading to a constellation of tissue abnormalities that has been referred to as the diabetes "ruling triumvirate." Targeted mutagenesis in mice has led to a critical reappraisal of the integrated physiology of insulin action. These studies indicate that insulin resistance in skeletal muscle and adipose tissue does not necessarily lead to hyperglycemia, so long as insulin sensitivity in other tissues is preserved. Additional data suggest a direct role of insulin signaling in beta-cell function and regulation of beta-cell mass, thus raising the possibility that insulin resistance may be the overarching feature of diabetes in all target tissues. I propose that we replace the original picture of a ruling triumvirate with that of a squabbling republic in which every tissue contributes to the onset of the disease.