| BackgroudIt is estimated that there are more than 400 million patients with diabetes in the world,most of which are type 2 diabetes,and according to the prediction by International Diabetes Federation,it will reach 642 million people by 2040.Diabetes has become a chronic disease that seriously impacts human health.Sleeve gastrectomy(SG)was originally used as a weight loss surgery for the treatment of morbid obese patients,and later found that it could also improve glycometabolism,which has now become one of the main metabolic surgery for the treatment of diabetes.Mitochondria-associated membranes(MAMs)are subcellular organelles closely linking endoplasmic reticulum to mitochondria.In recent years,more and more studies have found that structural imbalance of MAMs can lead to the increase of Ca2+ release from endoplasmic reticulum into mitochondria,causing mitochondrial calcium overload and mitochondrial dysfunction,finally resulting in insulin resistance.The aim of this study was to investigate the effect of SG on the insulin sensitivity and the expression of MAMs-related proteins in diabetic rats,and explore the effect of MAMs protein expression on the insulin sensitivity of diabetic rats after metabolic surgery.MethodsIntraperitoneal injection of low-dose streptozotocin combined with high-fat diet was used to establish diabetic rat models.The rats were divided into two groups:operation group(SG)and sham operation group(SHAM).Ten male Wistar rats were randomly assigned to each group.Food intake,body weight,oral glucose tolerance test(OGTT),insulin tolerance test(ITT)and steady-state model assessment of homeostasis model assessment(HOMA-IR)were measured before and after operation to evaluate glucose tolerance and insulin resistance.The expression of 1,4.5-trisphosphate receptor(IP3R).mitochondrial fusion protein 2(Mfn2).glucose-regulated protein 75(Grp75)and mitochondrial calcium uniporter(MCU)in MAMs was detected by western blot at 12 weeks postoperatively.ResultsCompared with the preoperative time,the food intake and body weight decreased in the first week after operation,and then gradually increased.At the 4th week and the 6th week after operation,the food intake and body weight of SG rats were lower than those of SHAM group,and the difference was statistically significant.The area under the curve of OGTT,ITT and HOMA-IR in SG group were lower than those in SHAM group(P<0.05).which showed the improvement of the glucose tolerance and insulin sensitivity after SG surgery.At the 12th week,the expression of IP3R.MCU and Mfn2.which related to the calcium channel and connection between endoplasmic reticulum and mitochondria,was lower in the SG group than that in the SHAM group(P<0.05).ConclusionsSG surgery can reduce the weight of diabetic rats.improve the level of glucose metabolism and increase insulin sensitivity.which changed early than that of food intake and bodyweight;at the same time,The expression of protein related to the calcium channel and connection between endoplasmic reticulum and mitochondria in the liver of diabetic rats was decreased,indicating that the decreased expression of proteins associated with calcium homeostasis in MAMs plays an important role in the increase of insulin sensitivity after sleeve gastrectomy in diabetic rats. |
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