Lipid receptors and islet function: therapeutic implications?
Lipid receptors and islet function: therapeutic implications?
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DOI：
10.1111/j.1463-1326.2009.01114.x
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发表时间：
2009-11
期刊：
影响因子：
--
通讯作者：
Poitout V
中科院分区：
文献类型：
--
作者：
Kebede MA;Alquier T;Latour MG;Poitout V
G蛋白偶联受体（GPCR）是目前市场上约30%药物的靶点。在过去的几年中，已经发现了许多在胰腺β细胞中表达并被脂质激活的GPCR。GPR 40被证明是由中长链脂肪酸（FA）激活。此后已经显示，GPR 40有助于葡萄糖诱导的胰岛素分泌的FA放大。尽管对于GPR 40激动剂或拮抗剂是否应该设计为新型2型糖尿病药物仍存在一些争议，但我们实验室和其他实验室获得的数据强烈表明，GPR 40激动可能代表一种有价值的治疗方法。GPR 119在胰腺β细胞和肠内分泌L细胞中表达，并通过其对β细胞的直接促胰岛素作用和通过FA刺激胰高血糖素样肽1（GLP-1）分泌来增加循环胰岛素水平。GPR 120在L细胞中表达，并且还被证明介导FA刺激的GLP-1释放。最后，GPR 41和GPR 43是短链FA的受体，并且可以通过脂肪因子分泌间接调节β细胞功能。虽然这些不同脂质受体的发现为药物开发开辟了新的和令人兴奋的研究途径，但有关其作用机制和生理作用的许多问题仍有待回答。
G-protein coupled receptors (GPCRs) are targets of approximately 30 % of currently marketed drugs. Over the last few years, a number of GPCRs expressed in pancreatic β cells and activated by lipids have been discovered. GPR40 was shown to be activated by medium- to long-chain fatty acids (FAs). It has since been shown that GPR40 contributes to FA amplification of glucose-induced insulin secretion. Although some controversy still exists as to whether GPR40 agonists or antagonists should be designed as novel type 2 diabetes drugs, data obtained in our laboratory and others strongly suggest that GPR40 agonism might represent a valuable therapeutic approach. GPR119 is expressed in pancreatic β cells and enteroendocrine L-cells, and augments circulating insulin levels both via its direct insulinotropic action on β cells and via FA stimulation of glucagon-like peptide 1 (GLP-1) secretion. GPR120 is expressed in L-cells and was also shown to mediate FA-stimulated GLP-1 release. Finally, GPR41 and GPR43 are receptors for short-chain FAs and may indirectly regulate β-cell function via adipokine secretion. While the discovery of these various lipid receptors opens new and exciting avenues of research for drug development, a number of questions regarding their mechanisms of action and physiological roles remain to be answered.
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影响因子：
3.9
作者：
Brownlie, Ruth;Mayers, Rachel M.;Smith, David M.
通讯作者：
Smith, David M.
影响因子：
4.8
作者：
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作者：
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DOI：
10.1152/ajpgi.1998.275.6.g1415
发表时间：
1998-12-01
影响因子：
4.5
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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