Regulation of hepatic glucose metabolism in health and disease.
Regulation of hepatic glucose metabolism in health and disease.
复制标题
调节健康和疾病中肝葡萄糖代谢。
DOI：
10.1038/nrendo.2017.80
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发表时间：
2017-10
期刊：
影响因子：
--
通讯作者：
Shulman GI
中科院分区：
文献类型：
--
作者：
Petersen MC;Vatner DF;Shulman GI
肝脏对于维持正常的葡萄糖稳态至关重要-它在禁食期间产生葡萄糖并在餐后储存葡萄糖。然而，这些肝脏过程在1型和2型糖尿病中失调，这种失衡导致空腹和餐后状态下的高血糖症。净肝葡萄糖产量是来自糖原生成、糖原分解、糖原合成、糖酵解和其他途径的葡萄糖通量的总和。在这篇综述中，我们讨论了这些肝脏葡萄糖通量的体内调节。特别是，我们强调的重要性，间接（肝外）控制肝再生和直接（肝）控制肝糖原代谢。我们还提出了2型糖尿病患者亚临床肝脏胰岛素抵抗进展为明显空腹高血糖的机制。还讨论了二甲双胍和胰岛素对肝糖原合成的控制以及脂质诱导的肝胰岛素抵抗在修饰肝糖原合成和净肝糖原合成通量中的作用。最后，我们考虑了针对脂肪肝、高胰高血糖素血症和脂肪分解的策略的治疗潜力。
The liver is crucial for the maintenance of normal glucose homeostasis — it produces glucose during fasting and stores glucose postprandially. However, these hepatic processes are dysregulated in type 1 and type 2 diabetes mellitus, and this imbalance contributes to hyperglycaemia in the fasted and postprandial states. Net hepatic glucose production is the summation of glucose fluxes from gluconeogenesis, glycogenolysis, glycogen synthesis, glycolysis and other pathways. In this Review, we discuss the in vivo regulation of these hepatic glucose fluxes. In particular, we highlight the importance of indirect (extrahepatic) control of hepatic gluconeogenesis and direct (hepatic) control of hepatic glycogen metabolism. We also propose a mechanism for the progression of subclinical hepatic insulin resistance to overt fasting hyperglycaemia in type 2 diabetes mellitus. Insights into the control of hepatic gluconeogenesis by metformin and insulin and into the role of lipid-induced hepatic insulin resistance in modifying gluconeogenic and net hepatic glycogen synthetic flux are also discussed. Finally, we consider the therapeutic potential of strategies that target hepatosteatosis, hyperglucagonaemia and adipose lipolysis.
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