2 型糖尿病发病机制中葡萄糖生成的调节。
Regulation of Glucose Production in the Pathogenesis of Type 2 Diabetes.
机构信息
Duke Molecular Physiology Institute, Duke University, Durham, NC, USA.
Division of Diabetes, Endocrinology, and Metabolism, Duke University, Durham, NC, USA.
出版信息
Curr Diab Rep. 2019 Aug 3;19(9):77. doi: 10.1007/s11892-019-1195-5.
PURPOSE OF REVIEW
Increased glucose production associated with hepatic insulin resistance contributes to the development of hyperglycemia in T2D. The molecular mechanisms accounting for increased glucose production remain controversial. Our aims were to review recent literature concerning molecular mechanisms regulating glucose production and to discuss these mechanisms in the context of physiological experiments and observations in humans and large animal models.
RECENT FINDINGS
Genetic intervention studies in rodents demonstrate that insulin can control hepatic glucose production through both direct effects on the liver, and through indirect effects to inhibit adipose tissue lipolysis and limit gluconeogenic substrate delivery. However, recent experiments in canine models indicate that the direct effects of insulin on the liver are dominant over the indirect effects to regulate glucose production. Recent molecular studies have also identified insulin-independent mechanisms by which hepatocytes sense intrahepatic carbohydrate levels to regulate carbohydrate disposal. Dysregulation of hepatic carbohydrate sensing systems may participate in increased glucose production in the development of diabetes.
目的综述
与肝胰岛素抵抗相关的葡萄糖生成增加是 T2D 患者高血糖发展的原因。但对于导致葡萄糖生成增加的分子机制仍存在争议。我们的目的是回顾关于调节葡萄糖生成的分子机制的最新文献，并结合人类和大动物模型中的生理实验和观察来讨论这些机制。
最近的发现
啮齿动物的基因干预研究表明，胰岛素可以通过直接作用于肝脏以及通过间接作用抑制脂肪组织脂肪分解和限制糖异生底物的输送来控制肝葡萄糖生成。然而，最近在犬模型中的实验表明，胰岛素对肝脏的直接作用在调节葡萄糖生成方面占主导地位。最近的分子研究也确定了肝细胞感知肝内碳水化合物水平以调节碳水化合物处理的胰岛素非依赖性机制。肝碳水化合物感知系统的失调可能参与了糖尿病发展过程中葡萄糖生成的增加。
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