G-protein-coupled receptor 40 (GPR40) expression and its regulation in human pancreatic islets: The role of type 2 diabetes and fatty acids
G-protein-coupled receptor 40 (GPR40) expression and its regulation in human pancreatic islets: The role of type 2 diabetes and fatty acids
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DOI：
10.1016/j.numecd.2009.02.008
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发表时间：
2010-01-01
影响因子：
3.9
通讯作者：
Lupi, R.
中科院分区：
文献类型：
--
作者：
Del Guerra, S.;Bugliani, M.;Lupi, R.
背景与目的：GPR 40是一种与中、长链脂肪酸（FFA）配对的膜结合受体。其急性激活增强β细胞的胰岛素分泌，而长期结合可能导致慢性暴露于FFA的有害作用。材料和方法：采用酶消化法和梯度分离法从20例非糖尿病（Ctrl）和13例2型糖尿病（T2 DM）多器官供体的胰腺中制备胰岛，并进行功能和分子研究。通过定性和定量PCR实验，在HI中显示mRNA表达。在T2 DM胰岛和对照胰岛中，与对照细胞相比，T2 DM细胞中的GPR 40 mRNA表达显著降低（p < 0.01），T2 DM胰岛和对照胰岛均预先暴露于1.0 mmol/l FFA（棕榈酸酯：油酸酯，2：1）24 h。葡萄糖刺激的胰岛素分泌与GPR 40的表达呈显著正相关。结论：人胰岛中GPR 40的表达受FFA的调控。T2 DM胰岛具有较低的GPR 40表达的发现，以及这些基因与胰岛素分泌的相关性，提高了GPR 40参与人类糖尿病β细胞功能障碍的可能性。(C)2009爱思唯尔有限公司版权所有。
Background and aims: GPR40 is a membrane-bound receptor paired with medium and long-chain fatty acids (FFA) as endogenous ligands. Its acute activation potentiates insulin secretion from beta cells, whereas prolonged binding might contribute to the deleterious effects of chronic exposure to FFA. Little information is available on the expression of GPR40 and its regulation in human islets (HI).Material and methods: HI were prepared by enzymatic digestion and gradient separation from the pancreas of 20 non-diabetic (Ctrl) and 13 type 2 diabetic (T2DM) multiorgan donors, and functional and molecular studies were then performed.Results: By qualitative and quantitative PCR experiments, mRNA expression was shown in HI. Both in T2DM islets and in Ctrl islets pre-exposed for 24 h to 1.0 mmol/l FFA (palmitate: oleate, 2: 1), GPR40 mRNA expression was significantly reduced (p < 0.01) in the T2DM cells as compared to Ctrl cells. A significant positive correlation was found between glucose-stimulated insulin secretion and GPR40 expression.Conclusions: These results show the expression of GPR40 in human pancreatic islets which are regulated by FFA. The finding that T2DM islets have a lower GPR40 expression, and the correlation of these genes with insulin secretion, raises the possibility of an involvement of GPR40 in human diabetes beta-cell dysfunction. (C) 2009 Elsevier B.V. All rights reserved.