DOI | 10.1038/s41586-020-2074-6
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| Glucagon stimulates gluconeogenesis by INSP3R1-mediated hepatic lipolysis |
| Liu, Xiaomeng1; Gao, Hongyan1; Ward, Joy E.2; Liu, Xiaorong3; Yin, Bing1; Fu, Tianda1; Chen, Jianhan3,4,5; Lovley, Derek R.2,4; Yao, Jun1,4
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| 2020-02-01
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发表期刊 | NATURE
![](/C666/image/waiting.gif) |
ISSN | 0028-0836
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EISSN | 1476-4687
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出版年 | 2020
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卷号 | 579期号:7798页码:279-+ |
文章类型 | Article
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语种 | 英语
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国家 | USA |
英文关键词 | 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.
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领域 | 地球科学
; 气候变化
; 资源环境
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收录类别 | SCI-E
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WOS记录号 | WOS:000518098200008
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WOS关键词 | RECEPTOR ANTAGONIST LY2409021
; GLUCOSE-HOMEOSTASIS
; INSULIN SENSITIVITY
; ENDOGENOUS GLUCAGON
; ADIPOSE-TISSUE
; IMMUNONEUTRALIZATION
; ACTIVATION
; MECHANISM
; PROTEIN
; OB/OB
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WOS类目 | Multidisciplinary Sciences
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WOS研究方向 | Science & Technology - Other Topics
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引用统计 |
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文献类型 | 期刊论文
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条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/281346
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专题 | 地球科学 资源环境科学 气候变化
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作者单位 | 1.Univ Massachusetts, Dept Elect & Comp Engn, Amherst, MA 01003 USA; 2.Univ Massachusetts, Dept Microbiol, Amherst, MA 01003 USA; 3.Univ Massachusetts, Dept Chem, Amherst, MA 01003 USA; 4.Univ Massachusetts, IALS, Amherst, MA 01003 USA; 5.Univ Massachusetts, Dept Biochem & Mol Biol, Amherst, MA 01003 USA
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推荐引用方式 GB/T 7714 |
Liu, Xiaomeng,Gao, Hongyan,Ward, Joy E.,et al. Glucagon stimulates gluconeogenesis by INSP3R1-mediated hepatic lipolysis[J].
NATURE,2020,579(7798):279-+.
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APA |
Liu, Xiaomeng.,Gao, Hongyan.,Ward, Joy E..,Liu, Xiaorong.,Yin, Bing.,...&Yao, Jun.(2020).Glucagon stimulates gluconeogenesis by INSP3R1-mediated hepatic lipolysis.NATURE,579(7798),279-+.
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MLA |
Liu, Xiaomeng,et al."Glucagon stimulates gluconeogenesis by INSP3R1-mediated hepatic lipolysis".NATURE 579.7798(2020):279-+.
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