Font Size: a A A

Study On The Mechanism Of GLP - 1 Pathway In Improving The Insulin Resistance Of Skeletal Muscle By Electroacupuncture

Posted on:2017-04-19Degree:DoctorType:Dissertation
Country:ChinaCandidate:B Y CaoFull Text:PDF
GTID:1104330482484951Subject:Acupuncture and Massage
Abstract/Summary:PDF Full Text Request
Objectives:The study aims at observing electro-acupuncture EX-B3’s effects on blood glucose, blood lipid, and insulin resistance of type 2 diabetic model rats, and exploring the possible onset mechanism of the intervention. It explains intervention effects of electro-acupuncture with nerve segment theory and neuroanatomy, and reveal the effect of electro-acupuncture on insulin resistance of type 2 diabetic rats’skeletal muscle with GLP-1-cAMP-PI3K-GLUT4 signal pathway. By doing so, the study provides evidence for treating type 2 diabetes with electro-acupuncture in clinics.Method:It takes high fat and high sugar diet combined with intraperitoneal injection of streptozocin as model preparation. Model animals were divided randomly into model group, electro-acupuncture EX-B3 group, electro-acupuncture BL-15 group,electro-acupuncture BL-23 group, and electro-acupuncture ST-36 group (n=12). Electro-acupuncture with 2Hz, 2mA continuous wave,20min/time,6 times/week,4 weeks was applied as intervention. Fasting blood glucose was tested before the intervention and during the 7th,14th,21st, and 28th day of the intervention. Oral glucose tolerance test was conducted before and after the whole intervention for calculation of area under curve of oral glucose tolerance test. After the intervention, rats were anaesthetize with pentobarbital sodium, and sacrificed. Serum was collected for test of total cholesterol, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol, and glucagon peptide-like 1 concentrations. Part of the pancreas was fixed and prepared as paraffin sections for HE staining and Masson staining, for observing of structural and morphological change of pancreatic B cells. Western blot was applied for test of GLP-1 receptor protein expression in the pancreas, and GLP-1 receptor, cAMP, PI3K (Y607), and GLUT4 protein expressions in skeletal muscle.Results:All the electro-intervention can more or less reduce fasting blood glucose of model rats. Among the interventions, electro-acupuncture EX-B3 can greatly reduce rats’ fasting blood glucose at the 21st and 28th day of the intervention (P<0.01, P<0.05). Electro-acupuncture on BL-15 can significantly reduce rats’blood glucose at the 14th and 21st day of the intervention (P<0.05, P<0.01). Besides, electro-acupuncture EX-B3 can also remarkably decrease model rats’ serum total cholesterol, low density lipoprotein cholesterol, and triglyceride contents (P<0.01, P<0.01, P<0.01), area under curve of oral glucose tolerance test (P<0.05), and insulin resistance index (P<0.01). Mechanism study of electro-acupuncture’s effect shows that electro-acupuncture can reduce model rats’ highly rocketed plasma GLP-1 content, greatly increase model rats’ significantly lowered pancreas GLP-1 receptor protein expression (P<0.05), remarkably decrease model rats’greatly increased skeletal muscle GLP-1 receptor protein expression (P<0.01), and effectively regulate PI3K (Y607) and GLUT4 protein expressions in the skeletal muscle.Conclusion:Model rats prepared by high fat and high sugar diet combined with intraperitoneal injection of streptozocin can simulate hyperglycemia, hyperlipidemia, and insulin resistance of type 2 diabetes patients. Electro-acupuncture EX-B3 can effectively decrease model rats’ highly rocketed blood glucose and blood lipid indices. The effect was mainly obtained by regulation of insulin resistance. And electro-acupuncture’s effect on skeletal muscle insulin resistance was partly achieved by regulation of GLP-1-cAMP-PI3K-GLUT4 signal pathway. Electro-acupuncture BL-15 and BL-23 have certain effects on model rats’ blood glucose and blood lipid indices. Among the two interventions, electro-acupuncture BL-15 focus on restoration of the structure and morphology of pancreatic B cells. While electro-acupuncture BL-23 mainly takes effects by regulating insulin resistance. Among the points this study selected, EX-B3 ranks the most effective, followed by BL-15, BL-23, and ST-36. The points differ in onset time, and strength and duration of the effects, indicating differences in onset mechanisms. Therefore, the points can be selected according to the onset characteristics in clinical treatment of type 2 diabetes.
Keywords/Search Tags:electro-acupuncture, skeletal muscle, glucose transporter 4, EX-B3, glucagon-like peptide-1
PDF Full Text Request
Related items