Yang H, Egan J M, Wang Y, Moyes C D, Roth J, Montrose M H, Montrose-Rafizadeh C
Laboratory of Clinical Physiology, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Am J Physiol. 1998 Sep;275(3):C675-83. doi: 10.1152/ajpcell.1998.275.3.C675.
The incretin hormone glucagon-like peptide-1 (GLP-1)-(7-36) amide is best known for its antidiabetogenic actions mediated via a GLP-1 receptor present on pancreatic endocrine cells. To investigate the molecular mechanisms of GLP-1 action in muscle, we used cultured L6 myotubes. In L6 myotubes, GLP-1 enhanced insulin-stimulated glycogen synthesis by 140% while stimulating CO2 production and lactate formation by 150%. In the presence of IBMX, GLP-1 diminished cAMP levels to 83% of IBMX alone. In L6 myotubes transfected with pancreatic GLP-1 receptor, GLP-1 increased cAMP levels and inhibited glycogen synthesis by 60%. An antagonist of pancreatic GLP-1 receptor, exendin-4-(9-39), inhibited GLP-1-mediated glycogen synthesis in GLP-1 receptor-transfected L6 myotubes. However, in parental L6 myotubes, exendin-4-(9-39) and GLP-1-(1-36) amide, an inactive peptide on pancreatic GLP-1 receptor, displaced 125I-labeled GLP-1 binding and stimulated glycogen synthesis by 186 and 130%, respectively. These results suggest that the insulinomimetic effects of GLP-1 in L6 cells are likely to be mediated by a receptor that is different from the GLP-1 receptor found in the pancreas.
肠促胰岛素激素胰高血糖素样肽-1（GLP-1）-（7-36）酰胺因其通过胰腺内分泌细胞上存在的GLP-1受体介导的抗糖尿病作用而最为人所知。为了研究GLP-1在肌肉中的作用分子机制，我们使用了培养的L6肌管。在L6肌管中，GLP-1使胰岛素刺激的糖原合成增加了140%，同时使二氧化碳产生和乳酸生成增加了150%。在存在异丁基甲基黄嘌呤（IBMX）的情况下，GLP-1将环磷酸腺苷（cAMP）水平降至仅使用IBMX时的83%。在转染了胰腺GLP-1受体的L6肌管中，GLP-1增加了cAMP水平并使糖原合成减少了60%。胰腺GLP-1受体拮抗剂艾塞那肽-4-（9-39）抑制了GLP-1受体转染的L6肌管中GLP-1介导的糖原合成。然而，在亲本L6肌管中，艾塞那肽-4-（9-39）和GLP-1-（1-36）酰胺（一种对胰腺GLP-1受体无活性的肽）分别取代了125I标记的GLP-1结合并使糖原合成增加了186%和130%。这些结果表明，GLP-1在L6细胞中的胰岛素模拟作用可能由一种不同于胰腺中发现的GLP-1受体的受体介导。
