The long-chain fatty acid receptor, GPR40, and glucolipotoxicity: investigations using GPR40-knockout mice

被引:39
|
作者
Brownlie, Ruth [1 ]
Mayers, Rachel M. [1 ]
Pierce, Jackie A. [1 ]
Marley, Anna E. [1 ]
Smith, David M. [1 ]
机构
[1] AstraZeneca Diabet & Obes Drug Discovery, Macclesfield SK10 4TG, Cheshire, England
关键词
beta-cell; fatty acid; glucolipotoxicity; G-protein-coupled receptor 40 (GPR40); islet of Langerhans;
D O I
10.1042/BST0360950
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
GPR40 (G-protein-coupled receptor 40) has been shown to be a physiologically relevant receptor for long-chain fatty acids. it is a family A G-protein-coupled receptor highly expressed in the beta-cell where it increases insulin secretion by signalling via G(q) and phospholipase C. Fatty acids are well known to mediate both acute stimulatory effects and chronic detrimental effects on the beta-cell. GPR40-transgenic and GPR40(-/-) animals have been important tools in studies of the metabolic effects of GPR40. In the present article, we review the literature on transgenic GPR40 models and present some of our own studies on the effects of a high-fat diet on the metabolic phenotype of GPR(-/-) mice. GPR40 ligands represent interesting novel therapies for Type 2 diabetes but it is presently unclear whether agonists or antagonists represent the best therapeutic approach.
引用
收藏
页码:950 / 954
页数:5
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