Cell Metabolism 2011 Lin英语教案.pdf

Cell Metabolism Review Hormonal Regulation of Hepatic Glucose Production in Health and Disease Hua V. Lin1 and Domenico Accili2,* 1Merck Research Laboratories, Rahway, NJ 07065, USA 2Columbia University College of Physicians and Surgeons, New York, NY10032, USA *Correspondence: da230@columbia.edu DOI 10.1016/j.cmet.2011.06.003 We review mechanisms that regulate production of glucose by the liver, focusing on areas of budding consensus, and endeavoring to provide a candid assessment of lingering controversies. We also attempt to reconcile data from tracer studies in humans and large animals with the growing compilation of mouse knockouts that display changes in glucose production. A clinical hallmark of diabetes, excessive glucose production remains key to its treatment. Hence, we attempt to integrate emerging pathways into the broader goal to rejuvenate the staid antidiabetic pharmacopeia. Introduction that regulation of gene transcription and HGP are all too often Hepatic glucose production (HGP) is a key physiological process conflated into a single process, with recurring interpretive that becomes altered in diabetic patients (Bogardus et al., 1984) errors. and represents the main target of the antihyperglycemic effect of Tracer studies in dogs have defined hormonal regulation of HGP biguanides (Stumvoll et al., 1995). The combination of tracer and in detail. As in the isolated rodent liver, HGP is exquisitely sensitive spectroscopy methods in humans, selective catheterization of to glucagon and insulin. Glucagon sets the basal tone, but insulin portal and hepatic veins in dogs during tracer studies, condi- trumps glucagon at any concentration—just as it does in vitro. tional knockouts and metabolic phenotyping in mice, and Both hormones affect primarily glycogenolysis by recip