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首页> 外文期刊>Journal of Cellular Physiology >Presence of a functional receptor for GLP-1 in osteoblastic cells, independent of the cAMP-linked GLP-1 receptor.
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Presence of a functional receptor for GLP-1 in osteoblastic cells, independent of the cAMP-linked GLP-1 receptor.

机译：GLP-1功能受体的存在成骨细胞的细胞,独立的cAMP-linked GLP-1受体。

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摘要

Glucagon-like peptide 1 (GLP-1) controls glucose metabolism in extrapancreatic tissues through receptors other than the pancreatic cAMP-linked GLP-1 receptor; also, GLP-1 induces an insulin- and PTH-independent bone anabolic action in insulin-resistant and type-2 diabetic rats. Here we searched for the presence and characteristics of GLP-1 receptors in osteoblastic MC3T3-E1 cells. [(125)I]-GLP-1 specific binding to MC3T3-E1 cells was time- and temperature-dependent, reaching maximal value at 30 min at 25 degrees C; in these conditions, [(125)I]-GLP-1 binding was dissociable, and displaced by GLP-1, partially by GLP-2, but not by exendin-4 (Ex-4), exendin-9 (Ex-9), glucagon or insulin; Scatchard analysis of the unlabeled GLP-1 data showed high and low affinity binding sites; cross-linking of GLP-1 binding revealed an estimated 70 kDa band, almost undetectable in the presence of 10(-6) M GLP-1. GLP-1, Ex-9, insulin or glucagon failed to modify cellular cAMP content, while GLP-2 and Ex-4 increased it. However, GLP-1 induced an immediate hydrolysis of glycosylphosphatidylinositols (GPIs) generating short-lived inositolphosphoglycans (IPGs), and an increase in phosphatidylinositol-3 kinase (PI3K) and mitogen activated protein kinase (MAPK) activities; Ex-4 also affected GPIs, but its action was delayed with respect to that of GLP-1. This incretin was found to decrease Runx2 but increased osteocalcin gene expression, without affecting that of osteoprotegerin or the canonical Wnt pathway activity in MC3T3-E1 cells which do not express the pancreatic GLP-1 receptor. Our data demonstrate for the first time that GLP-1 can directly and functionally interact with osteoblastic cells, possibly through a GPI/IPG-coupled receptor.
机译：Glucagon-like肽1 (GLP-1)控制血糖新陈代谢extrapancreatic组织通过胰腺cAMP-linked以外的受体GLP-1受体;和PTH-independent骨合成代谢作用胰岛素抵抗和2型糖尿病大鼠。我们寻找的存在和特征的glp - 1在成骨细胞的受体MC3T3-E1细胞。是时候,MC3T3-E1细胞与温度有关的,达到最大的价值在25摄氏度30分钟;[(125)我]-GLP-1绑定是可分离的,和由GLP-2 GLP-1流离失所,部分,但不是由exendin-4(例4)exendin-9 (Ex-9),胰高血糖素或胰岛素;GLP-1数据显示,高和低亲和力绑定网站;大约70 kDa乐队,几乎检测不到10(6)米GLP-1的存在。或胰高血糖素未能修改手机阵营内容,而GLP-2和练习4增加它。然而,GLP-1诱导立即水解glycosylphosphatidylinositols (gpi)生成短暂的inositolphosphoglycans (IPGs),和一个增加phosphatidylinositol-3激酶(PI3K)和有丝分裂原激活蛋白激酶(MAPK)活动;行动被推迟对GLP-1。这种肠促胰岛素发现减少Runx2但是增加骨钙素基因表达,没有osteoprotegerin或影响规范Wnt通路活动MC3T3-E1细胞不表达胰腺GLP-1吗受体。GLP-1可以直接和功能进行交互与成骨细胞的细胞,有可能通过GPI / IPG-coupled受体。

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