| Objective:To investigate the clinical efficacy of laparoscopic Roux-en-Y gastric bypass surgery in the treatment of obese type 2 diabetes mellitus patients with BMI>28 kg/m2.To study the effect on methylation level of PPARGCIA gene promoter and miR-143-3p level on insulin secretion in islet cells after receiving Roux-en-Y gastric bypass surgery for obese type 2 diabetes mellitus rats.Methods:This subject collected laparoscopic gastric bypass surgery performed in the First Affiliated Hospital of Soochow University from February 2012.The patients were followed up for the third and sixth months after surgery.There were 33 clinical cases of obese type 2 diabetes(BMI>28kg/m2).The changes of body weight,height,fasting blood glucose,glycosylated hemoglobin,triglyceride and total cholesterol were recorded before and 3 months and 6 months after surgery.We constructed a rat model of obese type 2 diabetes and performed RYGB on them.Their pancreatic islet cells were cultured after dissecting pancreas.The promoter methylation level of PPARGC1A gene was detected by Bisulfite sequencing PCR(BSP).To certify whether the correlation between the expression of PPARGC1A mRNA and the amount of insulin secretion,transfection of PPARGC1A-siRNA was used to test rats' islet cells by high glucose stimulation.The miRNAs were reverse transcribed by stem-loop method,and the expression level of miR-143-3p in islet cells was detected by real-time fluorescent quantitative PCR.To investigate the correlation between miR-143-3p and the amount of insulin secretion by high glucose-stimulated islet cells,the miR-143-3p mimetic and inhibitor were used to overexpress and knocked down miR-143-3p,respectively.Results:All patients were discharged smoothly after surgery.The BMI,fasting blood glucose,HbAlc and TG levels in the patients after surgery were significantly lower than those before surgery,while the TC values did not change much.After twelve months of follow-up,1 case was ineffective,41 cases were partially relieved,and 25 cases were completely relieved.The methylation level of PPARGC1A gene promoter in islet cells of obese type 2 diabetic rats increased,and the lower methylation level could be restored after gastric bypass surgery.The promoter methylation of PPARGC1A gene was negatively correlated with its relative expression level of mRNA,while the relative expression of PPARGC1A mRNA was positively correlated with the insulin secretion stimulated by high glucose(16.7mmol/L glucose).The expression of miR-143-3p increased in islet cells of obese type 2 diabetic rats,and the lower expression level was restored after gastric bypass surgery.The relative expression of miR-143-3p in rats was negatively correlated with the amount of insulin secreted by high glucose(16.7 mmol/L glucose),but not with the expression of PPARGC1A mRNA.Conclusions:(1)Laparoscopic Roux-en-Y gastric bypass surgery is a relatively safe and effective weight loss surgery.This surgery is extremely advantageous for patients with proper obesity type 2 diabetes.Laparoscopic Roux-en-Y gastric bypass surgery can safely and rapidly reduce the weight of obese patients with type 2 diabetes or even cure diabetes in obese type 2 diabetic patients.(2)RYGB may reverse the methylation expression level of PPARGC1A gene promoter in islet cells of obese type 2 diabetic rats.The decrease of methylation in the promoter region of PPARGC1A gene can effectively increase the expression of PPARGC1A mRNA and the insulin secretion of islet cells stimulated by high glucose(16.7mmol/L glucose).(3)RYGB can change the expression of miR-143-3p in islet cells of obese type 2 diabetic rats.The expression of miR-143-3p in rat islet cells affects the insulin secretion of islet cells stimulated by high glucose(16.7 mmol/L glucose).There was no significant correlation between the expression of miR-143-3p in rat islet cells and the expression of PPARGC1A mRNA. |
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