Montrose-Rafizadeh C, Yang H, Wang Y, Roth J, Montrose M H, Adams L G
Gerontology Research Center, National Institute on Aging, NIH, Baltimore, Maryland 21224-2780, USA.
J Cell Physiol. 1997 Sep;172(3):275-83. doi: 10.1002/(SICI)1097-4652(199709)172:3<275::AID-JCP1>3.0.CO;2-L.
Glucagon-like peptide-1 (7-36) amide (GLP-1), in addition to its well known effect of enhancing glucose-mediated insulin release, has been shown to have insulinomimetic effects and to enhance insulin-mediated glucose uptake and lipid synthesis in 3T3-L1 adipocytes. To elucidate the mechanisms of GLP-1 action in these cells, we studied the signal transduction and peptide specificity of the GLP-1 response. In 3T3-L1 adipocytes, GLP-1 caused a decrease in intracellular cAMP levels which is the opposite to the response observed in pancreatic beta cells in response to the same peptide. In 3T3-L1 adipocytes, free intracellular calcium was not modified by GLP-1. Peptide specificity was examined to help determine if a different GLP receptor isoform was expressed in 3T3-L1 adipocytes vs. beta cells. Peptides with partial homology to GLP-1 such as GLP-2, GLP-1 (1-36), and glucagon all lowered cAMP levels in 3T3-L1 adipocytes. In addition, an antagonist of pancreatic GLP-1 receptor, exendin-4 (9-39), acted as an agonist to decrease cAMP levels in 3T3-L1 adipocytes as did exendin-4 (1-39), a known agonist for the pancreatic GLP-1 receptor. Binding studies using 125I-GLP-1 also suggest that pancreatic GLP-1 receptor isoform is not responsible for the effect of GLP-1 and related peptides in 3T3-L1 adipocytes. Based on these results, we propose that the major form of the GLP receptor in 3T3-L1 adipocytes is functionally different from the pancreatic GLP-1 receptor.
胰高血糖素样肽-1（7-36）酰胺（GLP-1），除了其众所周知的增强葡萄糖介导的胰岛素释放的作用外，还被证明具有胰岛素样作用，并能增强3T3-L1脂肪细胞中胰岛素介导的葡萄糖摄取和脂质合成。为了阐明GLP-1在这些细胞中的作用机制，我们研究了GLP-1反应的信号转导和肽特异性。在3T3-L1脂肪细胞中，GLP-1导致细胞内cAMP水平降低，这与在胰腺β细胞中对同一肽的反应相反。在3T3-L1脂肪细胞中，细胞内游离钙不受GLP-1的影响。研究了肽特异性，以帮助确定3T3-L1脂肪细胞与β细胞中是否表达不同的GLP受体亚型。与GLP-1具有部分同源性的肽，如GLP-2、GLP-1（1-36）和胰高血糖素，均能降低3T3-L1脂肪细胞中的cAMP水平。此外，胰腺GLP-1受体拮抗剂艾塞那肽-4（9-39），与已知的胰腺GLP-1受体激动剂艾塞那肽-4（1-39）一样，作为激动剂降低3T3-L1脂肪细胞中的cAMP水平。使用125I-GLP-1的结合研究也表明，胰腺GLP-1受体亚型与GLP-1及相关肽在3T3-L1脂肪细胞中的作用无关。基于这些结果，我们提出3T3-L1脂肪细胞中GLP受体的主要形式在功能上与胰腺GLP-1受体不同。
