Functional expression of the rat glucagon-like peptide-I receptor, evidence for coupling to both adenylyl cyclase and phospholipase-C.
Functional expression of the rat glucagon-like peptide-I receptor, evidence for coupling to both adenylyl cyclase and phospholipase-C.
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DOI：
10.1210/endo.133.1.8391428
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发表时间：
1993-07
期刊：
影响因子：
4.8
通讯作者：
M. Wheeler;M. Lu;J. S. Dillon;X. Leng;Chuan Chen;A. E. Boyd
中科院分区：
文献类型：
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作者：
M. Wheeler;M. Lu;J. S. Dillon;X. Leng;Chuan Chen;A. E. Boyd
在人类中，胰高血糖素样肽- i -(7-37) [GLP-I-(7-37)]是最有效的内源性胰岛素刺激激素。虽然GLP-I-(7-37)刺激的β细胞胰岛素分泌与cAMP积累增加有关，但对该肽使用的信号转导途径知之甚少。利用cDNA编码高亲和大鼠GLP-I-(7-37)受体[Kd = 4.1 nM]；在猴肾细胞系（COS-7）中表达GLP-I-(1-36)酰胺]的Kd = 1微米，我们已经证明该受体不仅与腺苷酸环化酶偶联，而且与游离胞质钙水平（[Ca2+]i）的增加有关。GLP-I-(7-37)以剂量依赖的方式增加cAMP和[Ca2+]i，并且具有相同的效价（ED50 = 2.0 nM）。[Ca2+]i增加的主要来源被发现是通过与磷酸肌醇周转增加相关的细胞内Ca2+池的释放。Northern blot杂交研究表明，glp - 1 -(7-37)受体基因在胰岛和肺中表达量相对较高，但在脑、肝、肾和骨骼肌中表达量也较低。本研究证实单一GLP-I受体可以通过多种g蛋白偶联信号通路介导GLP-I-(7-37)的作用，包括腺苷酸环化酶系统、磷脂酶-c和[Ca2+]i的变化。
In man, glucagon-like peptide-I-(7-37) [GLP-I-(7-37)] is the most potent endogenous insulin-stimulating hormone. Although GLP-I-(7-37)-stimulated insulin secretion from the beta-cell is associated with an increase in cAMP accumulation, little is known about the signal transduction pathways used by this peptide. Using a cDNA encoding a high affinity rat GLP-I-(7-37) receptor [Kd = 4.1 nM for GLP-I-(7-37); Kd = 1 microM for GLP-I-(1-36) amide] expressed in a monkey kidney cell line (COS-7), we have demonstrated that the receptor is not only coupled to adenylyl cyclase, but is associated with an increase in the free cytosolic calcium level ([Ca2+]i). GLP-I-(7-37) increased both cAMP and [Ca2+]i in a dose-dependent manner and with equal potency (ED50 = 2.0 nM). The major source of the increased [Ca2+]i was found to be through the release of intracellular pools of Ca2+ associated with an increase in phosphoinositol turnover. Northern blot hybridization studies demonstrated that the GLP-I-(7-37) receptor gene was expressed in relatively high abundance in pancreatic islets and lung, but was also expressed at lower levels in the brain, liver, kidney, and skeletal muscle. This study establishes that a single GLP-I receptor species can mediate the effects of GLP-I-(7-37) through multiple G-protein-coupled signaling pathways, including the adenylyl cyclase system, phospholipase-C, and changes in [Ca2+]i.