Biguanides suppress hepatic glucagon signalling by decreasing production of cyclic AMP

Russell A. Miller, Qingwei Chu, Jianxin Xie, Marc Foretz, Benoit Viollet & Morris J. Birnbaum

Glucose production by the liver is essential for providing a substrate for the brain during fasting. The inability of insulin to suppress hepatic glucose output is a major aetiological factor in the hyperglycaemia of type-2 diabetes mellitus and other diseases of insulin resistance1, 2. For fifty years, one of the few classes of therapeutics effective in reducing glucose production has been the biguanides, which include phenformin and metformin, the latter the most frequently prescribed drug for type-2 diabetes3. Nonetheless, the mechanism of action of biguanides remains imperfectly understood. The suggestion a decade ago that metformin reduces glucose synthesis through activation of the enzyme AMP-activated protein kinase (AMPK) has recently been challenged by genetic loss-of-function experiments4. Here we provide a novel mechanism by which metformin antagonizes the action of glucagon, thus reducing fasting glucose levels. In mouse hepatocytes, metformin leads to the accumulation of AMP and related nucleotides, which inhibit adenylate cyclase, reduce levels of cyclic AMP and protein kinase A (PKA) activity, abrogate phosphorylation of critical protein targets of PKA, and block glucagon-dependent glucose output from hepatocytes. These data support a mechanism of action for metformin involving antagonism of glucagon, and suggest an approach for the development of antidiabetic drugs.

• 以上资料由西亚试剂：http://www.xiyashiji.com/ 提供此产品的详细信息如密度,含量,分子式,分子量等均可在西亚官网查询   
• 相关产品如诺卡氏菌液(-)-樟脑神经鞘磷脂,从牛脑所得 杨梅苷愈创奥IAPN-叔丁基苯硫腈氯化物4-溴苯基五氟化硫色胺盐酸盐4-溴噻吩-2-甲醛纤维素粉 7-(二甲基氨基)-4-三氟甲基香豆素邻硝基苯肼盐酸盐3,3'-二氨基联苯胺四盐酸盐水合物美伐他汀丁卡因阿卡明全氟辛基季胺碘化物布西拉明硫酸多粘菌素B益母草浸膏黄苓干膏 L-2,3-二氨基丙酸盐酸盐黄糊精EB替代品(GoldView)等均有销售.欢迎订购