Barakat Ghinwa, Moustafa Mohamed E, Khalifeh Ibrahim, Hodroj Mohammad H, Bikhazi Anwar, Rizk Sandra
Department of Biological Sciences, Faculty of Science, Beirut Arab University, Beirut, Lebanon.
Department of Biochemistry, Faculty of Science, Alexandria University, Alexandria, Egypt.
J Physiol Biochem. 2016 Aug;73(3):387-394. doi: 10.1007/s13105-017-0565-1. Epub 2017 Jun 7.
The mechanisms by which exendin-4 and selenium exert their antidiabetic actions are still unclear. Here, we investigated the effects of exendin-4 or selenium administration on the expression of glucagon-like peptide-1 receptor (GLP-1R), insulin receptor substrate-1 (IRS-1), and preproinsulin in the pancreas of diabetic rats. Diabetes was induced by streptozotocin administration. Diabetic rats were injected intraperitoneally with 0.03 μg exendin-4/kg body weight/daily or treated with 5 ppm selenium in drinking water for a period of 4 weeks. GLP-1R and IRS-1 levels were decreased while the level of preproinsulin messenger RNA (mRNA) was increased in the pancreas of diabetic untreated rats, as compared to that in control rats. Treatment of diabetic rats with exendin-4 increased protein and mRNA levels of GLP-1R, and IRS-1, and the mRNA level of preproinsulin in the pancreas, as compared to their levels in diabetic untreated rats. Selenium treatment of diabetic rats increased the pancreatic mRNA levels of GLP-1R, IRS-1, and preproinsulin. Exendin-4 or selenium treatment of diabetic rats also increased the numbers of pancreatic islets and GLP-1R molecules in the pancreas. Therefore, exendin-4 and selenium may exert their antidiabetic effects by increasing GLP-1R, IRS-1, and preproinsulin expression in the pancreas and by increasing the number of pancreatic islets.
艾塞那肽-4和硒发挥抗糖尿病作用的机制尚不清楚。在此，我们研究了给予艾塞那肽-4或硒对糖尿病大鼠胰腺中胰高血糖素样肽-1受体（GLP-1R）、胰岛素受体底物-1（IRS-1）和胰岛素原的表达的影响。通过给予链脲佐菌素诱导糖尿病。糖尿病大鼠每天腹腔注射0.03μg艾塞那肽-4/千克体重，或饮用含5ppm硒的水进行为期4周的治疗。与对照大鼠相比，未经治疗的糖尿病大鼠胰腺中GLP-1R和IRS-1水平降低，而胰岛素原信使核糖核酸（mRNA）水平升高。与未经治疗的糖尿病大鼠相比，用艾塞那肽-4治疗糖尿病大鼠可增加胰腺中GLP-1R、IRS-1的蛋白质和mRNA水平以及胰岛素原的mRNA水平。用硒治疗糖尿病大鼠可增加胰腺中GLP-1R、IRS-1和胰岛素原的mRNA水平。用艾塞那肽-4或硒治疗糖尿病大鼠还可增加胰腺中胰岛数量和GLP-1R分子数量。因此，艾塞那肽-4和硒可能通过增加胰腺中GLP-1R、IRS-1和胰岛素原的表达以及增加胰岛数量来发挥其抗糖尿病作用。
