Regulation Of Glucagon-Like Peptide 1 On The Function Of Isolated Rat Islets

Objective: To observe the effect of glucagon-like peptide 1(GLP-1) on glucose-stimulated insulin secretion, on the regulation of transcription factors expression related to the differentiation & maturation of (3 cell and on the proliferation & anti-apoptotic effects in isolated rat pancreatic islets in order to investigate the regulatory mechanism of GLP-1 on pancreatic islets and illustrate the role of GLP-1 in the treatment of the diabetes mellitus. Methods: (1) The isolated rat islets were co-cultured with 10nmol/L GLP-1 for 1, 3 & 5 days. At the end of each day, glucose-stimulated insulin secretion test was performed and the supernatants of the islets were collected to examine the insulin levels in 0, 10, 20, 60 min by radioimmunoassay. (2) At the end of day 1, 3 and 5, total cellular RNA was extracted, and the gene expressions of insulin, GLUT2 & some transcription factors were detected by RT-PCR. (3) Rat insulinoma cell strain RINm5f was cultured with different concentrations of GLP-1 or with 10nmol/L GLP-1 for various periods. Cell proliferation was assessed by MTT colorimetric assay. (4) The protective effect of GLP-1 on the apoptosis of cell strain RINm5f induced by IL-1β was observed by flow cytometry. The regulation of GLP-1 on the BAX & Bcl-2 gene expressions in isolated rat islets was detected by RT-PCR.Results: (1) After co-cultured with GLP-1, both the baseline and glucose-stimulated insulin secretion increased. (2)Compared with the control group, the gene expression of insulin, GLUT2 and some transcription factors were all increased in a time-dependent manner after co-cultured with GLP-1. (3) After co-cultured with GLP-1, the OD values were elevated in a dose & time-dependent fashion. (4) GLP-1 could reduce cell apoptosis induced by IL-1β. Moreover GLP-1 stimulated the Bcl-2 gene expression, while inhibited the BAX gene expression in a time-dependent manner.Conclusions: (1) GLP-1 could improve insulin secretion and promote the gene expression of insulin and GLUT2 in pancreatic islets. (2) GLP-1 could promote the gene expression of PDX-1, PAX-6 and NKx2.2. (3) GLP-1 increases the proliferation and reduces the apoptosis of pancreatic islets, at least partially, by regulating apopotosis-related gene expression.