The G-protein-coupled receptor 40 family (GPR40-GPR43) and its role in nutrient sensing
The G-protein-coupled receptor 40 family (GPR40-GPR43) and its role in nutrient sensing
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DOI：
10.1042/bst0340770
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发表时间：
2006-11-01
影响因子：
3.9
通讯作者：
Jayawickreme, C. K.
中科院分区：
文献类型：
--
作者：
Covington, D. K.;Briscoe, C. A.;Jayawickreme, C. K.
最近的去磷酸化努力已经将G蛋白偶联受体GPR 40、GPR 41和GPR 43与作为内源性配体的脂肪酸配对。虽然羧酸在历史上被认为是疾病的燃料来源和生物标志物，但这些研究表明脂肪酸可以在细胞表面水平上作为信号分子。该受体亚家族共享约。成员之间的同一性为30%，配体活性之间的交叉有限。胰腺β细胞、脂肪库和胃肠道内的一般表达模式推断参与能量源识别、吸收、储存和/或代谢。由中链和长链脂肪酸激活的GPR 40已被证明可增强β细胞的胰岛素分泌，并被假设参与慢性脂肪酸暴露对β细胞功能的有害影响。据报道，GPR 41和GPR 43分别通过短链脂肪酸激活来刺激瘦素释放和脂肪形成。这些共同的主题暗示GPR 40、GPR 41和GPR 43在代谢疾病如糖尿病、肥胖和代谢综合征中发挥重要作用。
Recent deorphanization efforts have paired the G-protein-coupled receptors GPR40, GPR41 and GPR43 with fatty acids as endogenous ligands. While carboxylic acids have been historically known to serve as fuel sources and biomarkers of disease, these studies demonstrate that fatty acids can act as signalling molecules at the cell-surface level. This receptor subfamily shares approx. 30% identity among members, with some limited cross-over between ligand activities. Generalized expression patterns within the pancreatic beta-cell, adipose depots and the gastrointestinal tract infer involvement in energy source recognition, absorption, storage and/or metabolism. GPR40, activated by medium and long-chain fatty acids, has been shown to potentiate insulin secretion at the beta-cell, and has been hypothesized to participate in the detrimental effects of chronic fatty acid exposure on beta-cell function. GPR41 and GPR43 have been reported to stimulate leptin release and adipogenesis respectively via activation by short-chain fatty acids. These common themes implicate GPR40, GPR41 and GPR43 in playing significant roles in metabolic diseases, such as diabetes, obesity and the metabolic syndrome.