| Summary: | 碩士 === 中山醫學大學 === 營養學研究所 === 100 === Diabetes Melitus (DM) is one of the most popular chronic diseases in the world. Poor glycemic control is a known major factor that leads to diabetic complications and is attributed to increased oxidative stress. According to previous studies, Morus alba leaves and its extract (ME) possesses hypoglycemic effect with 1-deoxynojirimycin (1-DNJ) as a functional compound. However, the mechanisms underlying which ME and 1-DNJ lowering blood glucose level remain to be clarified. It is also not known how ME and 1-DNJ affect the development of DM nephropathy. The aim of this study is to investigate the antidiabetic effect of ME and 1-DNJ including their effect on the development of diabetic nephropathy and the related mechanisms. Male Wistar rats were injected with streptozotocin (65 mg/kg BW, i.v.) to induce DM. Control rats were injected with citrate buffer solution. 7 days after induction, the DM rats were assigned randomly to six groups and were treated with 1, 3, 10, 30 mg/kg BW of ME, 30 mg/kg BW of DNJ or vehicle (d.d. H2O; 2 ml/kg BW) for a week. Normal control rats also received vehicle. OGTT was carried out at 7 or 11 days and ITT was carried out at 11 days after induction. At 14 days after induction, rats were killed with CO2 and organ/tissue samples collected for various biochemical analyses and the determination of oxidative stress and renal function. On the DM rats all doses of ME and 1-DNJ significantly ameliorated fasting blood glucose and AUC of glucose during OGTT period chronically and ME also showed such effect acutely. All doses of ME and 1-DNJ significantly increased peripheral and pancreatic levels of insulin and improved HOMA-IR in DM rats. Ten and 30 mg/kg of ME improved insulin-induced lowering of blood glucose level in DM rats. In the other hand, all doses of ME and 1-DNJ significantly reversed increased TBARS of the pancreas, kidneys, livers, muscles and peripheral blood in DM as well as decreased GRd activity of the pancreas and kidneys in DM. In addition, 1-DNJ significantly reversed lowered GPx and GRd activity of the livers and muscles in DM. ME at 30 mg/kg significantly reversed lowered GPx activity of the muscle, at 10 to 30 mg/kg significantly reversed lowered GRd activity of the kidneys, at 1 mg/kg significantly reversed lowered GRd activity of of the livers, at 3 to 30 mg/kg significantly reversed lowered GRd activity of the muscles. All ME doses and 1-DNJ significantly decreased NO content of the pancreas, kidneys, livers,and muscles in DM. The indices of renal function, including BUN, CCR, and GFR were all ameliorated by all doses of ME and 1-DNJ. In addition, 30 mg/kg of ME and 1-DNJ improved glomerular morphology of the kidneys and lowered blood pressure in DM. In conclusion, ME and 1-DNJ improved insulin secretion and insulin sensitivity and attenuated the development of diabetic nephropathy. The antidiabetic effects of ME and 1-DNJ is at least partly due to the amelioration of the increased oxidative stress in DM.
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