Sharabi Kfir, Tavares Clint D J, Rines Amy K, Puigserver Pere
Department of Cancer Biology, Department of Cell Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Department of Cancer Biology, Department of Cell Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Mol Aspects Med. 2015 Dec;46:21-33. doi: 10.1016/j.mam.2015.09.003. Epub 2015 Nov 5.
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 glycemia 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.
在禁食或营养物质供应过剩期间，将血糖浓度维持在相对狭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生成之间的复杂平衡来实现的，以维持恒定的葡萄糖浓度。肝脏在维持正常的全身血糖水平方面发挥着主要作用，它通过调节从头合成葡萄糖（糖异生）和糖原分解（糖原olysis）的过程，从而控制肝脏葡萄糖释放水平。肝脏葡萄糖生成（HGP）的异常调节会导致有害的临床结果，而过量的HGP是2型糖尿病（T2DM）中观察到的高血糖的主要促成因素。事实上，将血糖尽可能调整到非糖尿病范围是T2DM患者医学治疗的首要目标，目前在临床上主要通过抑制HGP来实现。在这里，我们回顾了响应营养和激素信号控制HGP的分子机制，并讨论了这些信号在T2DM中是如何改变的。
