GPR40,游离脂肪酸受体胰腺β细胞,调节胰岛素分泌。
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伊藤Y, Hinuma年代
GPR40,游离脂肪酸受体胰腺β细胞,调节胰岛素分泌。
乙醇研究》2005年10月,33 (2):171 - 3。Epub 2005年10月6日。
- PubMed ID
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16214394 (在PubMed]
- 文摘
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GPR40最初是由简并PCR从人类基因组DNA分离。从不同的物种,我们孤立GPR40的互补和准确地分析其mRNA表达在大鼠组织中,并发现GPR40高度表达在大鼠胰腺的胰岛β细胞。细胞表面受体(即相比。choresistokinin受体,glucagon-like peptide-1受体和磺酰脲类受体)已知的主要表达在胰腺β细胞,GPR40mRNA在mRNA表达水平与这些受体。此外,所有的胰腺β细胞线,我们检查,表示GPR40mRNA在显著水平。鼠标的最高表达检测βMIN6细胞线。揭示GPR40的功能,我们寻找GPR40的配体筛选超过1500种化合物。结果我们发现,CHO细胞表达GPR40专门对游离脂肪酸(远期运费协议),也就是说,海拔胞内钙(2 +)中检测出这些细胞。在远期运费协议测试中,发现了明显的刺激活动C12 - 16-length饱和远期运费协议(例如,月桂酸,肉豆蔻酸,棕榈酸)和C18 -和C22-length不饱和远期运费协议(如油酸、反油酸,亚油酸,a-linolenic酸,g-linolenic酸、花生四烯酸、二十碳五烯酸和二十二碳六烯酸)在EC(50)的微摩尔范围。我们发现远期运费协议引起Ca(2 +)流入和激活MAP激酶在CHO细胞表达GPR40。 As it is known that the increase of intracellular Ca(2+) promotes insulin secretion, we expected the stimulation of FFAs through GPR40 would promote insulin secretion from pancreatic beta cells. As we expected, FFAs induced glucose-stimulated insulin secretion (GSIS) in MIN6 cells. Our results indicate that GPR40 is a cell-surface receptor for FFAs and regulates insulin secretion from pancreatic beta cells. FFAs are known not only to provide an important energy source as nutrients for the body but also to act as signaling molecules in various cellular processes including insulin secretion. However, the molecular mechanism behind the relationship between insulin secretion and FFAs is little understood. We believe that the discovery of a cell-surface FFA receptor on pancreatic beta cells will provide a clue to resolve the relation between FFAs and insulin secretion, and thus eventually lead to the development of anti-diabetic drugs.