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美国启动社区气候灾害风险评估门户网站 快报文章
气候变化快报,2022年第19期
作者:  王田宇 刘燕飞
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Climate Hazards  CMRA Portal  Future Climate-related Hazards  
欧盟启动气候与健康门户网站 快报文章
气候变化快报,2021年第6期
作者:  刘燕飞
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European Climate and Health Observatory  Climate change  portal  Climate-ADAPT  
Glucagon stimulates gluconeogenesis by INSP3R1-mediated hepatic lipolysis 期刊论文
NATURE, 2020, 579 (7798) : 279-+
作者:  Liu, Xiaomeng;  Gao, Hongyan;  Ward, Joy E.;  Liu, Xiaorong;  Yin, Bing;  Fu, Tianda;  Chen, Jianhan;  Lovley, Derek R.;  Yao, Jun
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Although it is well-established that reductions in the ratio of insulin to glucagon in the portal vein have a major role in the dysregulation of hepatic glucose metabolism in type-2 diabetes(1-3), the mechanisms by which glucagon affects hepatic glucose production and mitochondrial oxidation are poorly understood. Here we show that glucagon stimulates hepatic gluconeogenesis by increasing the activity of hepatic adipose triglyceride lipase, intrahepatic lipolysis, hepatic acetyl-CoA content and pyruvate carboxylase flux, while also increasing mitochondrial fat oxidation-all of which are mediated by stimulation of the inositol triphosphate receptor 1 (INSP3R1). In rats and mice, chronic physiological increases in plasma glucagon concentrations increased mitochondrial oxidation of fat in the liver and reversed diet-induced hepatic steatosis and insulin resistance. However, these effects of chronic glucagon treatment-reversing hepatic steatosis and glucose intolerance-were abrogated in Insp3r1 (also known as Itpr1)-knockout mice. These results provide insights into glucagon biology and suggest that INSP3R1 may represent a target for therapies that aim to reverse nonalcoholic fatty liver disease and type-2 diabetes.