The Effects Of Moderate-intensity Exercise On The Promoting Of Secretion Of Insulin In Diabetic Rats By Glipizide And Mechanism

Objective:This study investigated the effects of exercise on the promoting of secretion of insulin and the reducing blood glucose by glipizide, at the same time, explored the possible mechanism. The purpose of the study was to clarify whether exercise combined with sulfonylurea drugs can have the role in increasing the effect and reducing the toxicity:reduce the secretion of insulin promoted by sulfonylurea drugs, improve the compensatory situation of islet β cell; increase the hypoglycemic effect of sulfonylurea drugs.Methods:8-week-old male SD rats were injected of STZ (30 mg/kg) through the method of intraperitoneal injection. After the diabetes was induced, all diabetic rats were arranged an adaptive treadmill training every day for a week.80 diabetic were selected and randomly divided into 4 groups:DM exercise plus glipizide group (DSG, n= 20), DM glipizide group (DG, n=20), DM exercise group (DS, n=20), DM control group (D, n=20). After 12 hours of fasting, rats in DGS group and DG group received oral gavage of glipizide (lmg/kg), the rest two groups received oral gavage of same volume of saline, there hours after gavage administration, DSG group and DS group exercised for 43 minutes (28m/min, rest 30 s every 5 mins),2、4、7 and 10 hours after gavage administration, five rats were killed in each group and collected blood、 liver、pancreas、kidney、skeletal muscle (gastrocnemius), DS group and D group only collected blood.Results:Take a one-time intraperitoneal injection of STZ (30 mg/kg) established SD rats diabetes model successfully. Experimental results show that:immediately after exercise, the drug concentration in plasma(P<0.01)、liver(P<0.01)、kidney (P<0.05) and pancreas (P<0.01) decreased significantly. After a break of 3 hours, the drug concentration in plasma increased significantly(P<0.01); change of it in gastrocnemius shown an opposite trend:elevated after exercise (P<0.01), ecreased after the break(P<0.01); 2 hours after gavage, the drug can significantly lower blood glucose (P<0.01),4、 7 and 10 hours after gavage, the effect continued without significant differences; blood glucose did not decrease immediately after exercise in DS group, however,3 hours after exercise, it shown a significant hypoglycemic action(P<0.01); 6 hours after exercise, blood glucose still decreased significantly(P<0.05); exercise combined with glipizide can control blood glucose effectively and smoothly, its action appeared immediately after exercise(P<0.05), which remained 6 hours after exercise (P<0.05); 2 hours after gavage, secretion of insulin increased(P<0.01), the effect lasted until 10 hours(P<0.01); exercise can inhibit the stimulation of insulin by glipizide significantly(P<0.01).Conclusions:(1)The SD rats were established into diabetes model by single intraperitoneal injection of STZ(30mg/kg); (2) Changes of drug concentration in plasma and tissue after exercise can impact the efficacy of glipizide directly, it reflected the mechanism of the redistribution of blood after exercise, this is also the focus of future research to provide guidance of reasonable exercise and rational drug use for patients; (3)Glipizide can promote the secretion of insulin, at the same time it has good hypoglycemic action.; (4)Single moderate-intensity treadmill exercise had sustained hypoglycemic effect on diabetic rats; (5)Exercise combined with glipizide had more stable and durable action on the blood glucose, they had a synergistic effect; (6)Exercise inhibited the stimulation of insulin by glipizide and protect the β cells indirectly, on this way, exercise can slow the secondary failure of sulfonylurea drugs.