Molecular pathophysiology of hepatic glucose production.
Molecular pathophysiology of hepatic glucose production.
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DOI：
10.1016/j.mam.2015.09.003
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发表时间：
2015-12
影响因子：
10.6
通讯作者：
Puigserver P
中科院分区：
文献类型：
--
作者：
Sharabi K;Tavares CD;Rines AK;Puigserver P
在禁食或过量营养供应期间将血糖浓度维持在相对较窄的范围内对生物体的生存至关重要。这是通过葡萄糖摄取和内源性葡萄糖产生之间的复杂平衡来实现的，以维持恒定的葡萄糖浓度。肝脏通过调节从头葡萄糖产生（糖原生成）和糖原分解（糖原分解）的过程，从而控制肝脏葡萄糖释放的水平，在维持正常的全身葡萄糖水平方面发挥重要作用。肝葡萄糖生成（HGP）的异常调节可导致有害的临床结果，并且过量的HGP是2型糖尿病（T2DM）中观察到的高血糖症的主要促成因素。事实上，将高血糖调节至尽可能接近非糖尿病范围是T2DM患者药物治疗的首要目标，目前在临床上主要通过抑制HGP来实现。在这里，我们回顾了控制HGP响应营养和激素信号的分子机制，并讨论了这些信号在T2DM中是如何改变的。
Maintaining blood glucose concentration within a relatively narrow range through periods of fasting or excess nutrient availability is essential to the survival of the organism. This is achieved through an intricate balance between glucose uptake and endogenous glucose production to maintain constant glucose concentrations. The liver plays a major role in maintaining normal whole body glucose levels by regulating the processes of de novo glucose production (gluconeogenesis) and glycogen breakdown (glycogenolysis), thus controlling the levels of hepatic glucose release. Aberrant regulation of hepatic glucose production (HGP) can result in deleterious clinical outcomes, and excessive HGP is a major contributor to the hyperglycemia observed in Type 2 diabetes mellitus (T2DM). Indeed, adjusting glycaemia as close as possible to a non-diabetic range is the foremost objective in the medical treatment of patients with T2DM and is currently achieved in the clinic primarily through suppression of HGP. Here, we review the molecular mechanisms controlling HGP in response to nutritional and hormonal signals and discuss how these signals are altered in T2DM.