| Study oneThe effect of Jiaotai pill on treatment of type 2 diabetes in combination with exerciseBackground:The pathogenesis of type 2 diabetes mellitus(T2DM)is complex,and adipose cytokines such as adiponectin have been thought to play an important role.The latest domestic and international guidelines for diabetes management recommended lifestyle interventions,including exercise,throughout the whole process.Our previous studies have found that exercise decreased blood glucose significantly in diabetic patients.However,it is difficult for patients to maintain long-term exercise.Recently,the effect of traditional Chinese medicine(TCM)on T2DM has been addressed.Among them,Jiaotai pill,,has been recognized as an typical decoction in the treatment of type 2 diabetes by its simplication,safety and effectivity,though the underlying mechanism is still unclear,particularly when combined with exercises.Objectives:To investigate the clinical effect and underlying mechanism of Jiaotai pill in combination with exercise on serum glucose and adiponectin in patients with type 2 diabetes mellitus.Methods:Sixty patients with T2DM were randomly divided into three groups,control group(n=18),exercise group(n=21)and combination group of Jiaotai pill and exercise(n=21).All the patients maintained the original hypoglycemic regimen.On this basis,the control group kept on current life style,meanwhile,exercise group and combination group received exercise 4 days a week,30 minutes each time.Additionally,Jiaotai pill was given orally in the combination group everyday.Totally,the interventions lasted 12 weeks.TCM syndrome score,blood glucose,insulin,adiponectin,liver and kidney function,and blood lipid were observed before and after treatment among three groups.The homeostasis model assessment β(HOMA-β)was calculated simultaneously as well.Results:During the treatment,one and two cases dropped in the exercise group(n=20)and the combination group(n=19),respectively.There were no significant differences in age,sex,weight,waist circumference,body mass index(BMI),TCM syndrome scores,HbA1c,HOMA-β index,and adiponectin at baseline among three groups.After the treatment,no significant differences in body weight,waist circumference,BMI among three groups were documented.The TCM syndrome scores in combination group and exercise group were significantly decreased(p<0.05),and the combination group decreased more significantly than exercise group(p<0.05).The effectivity rate of the combination group was significantly higher than that of control group or exercise group(p<0.05).HbA1c decreased and HOMA-β index increased significantly in combination group(p<0.05)and exercise group,with a larger amplitude in the combination group(p<0.05).The serum adiponectin in combination group and exercise group increased significantly after treatment,and even significantly higher in the combination group when compared with the exercise group(p<0.05).Conclusions:1.The combination of Jiaotai pill and exercise therapy exerts greater effects on theimprovement of the TCM syndrome score,fasting blood glucose,and β cell function of patients with T2DM.2.The combination of Jiaotai pill and exercise might protect islet β cell function by increasing the level of serum adiponectin.Study twoUnderlying mechanism of protective effect of Jiaotai pill on(3 cell function by combining with exercise in type 2 diabetic mice based on Sirt1/FoxO1/APN pathwayBackground:Our clinical study found that the therapeutic effect of Jiaotai pill by combining with exercise on T2DM was associated with the elevation of serum adiponectin.However,the underlying mechanism is still unclear.The silent information regulation factor-related enzyme 1(Sirt1)is an important regulating factor and participates in regulation of various signaling pathways.Sirt1 increases the expression of adiponectin in transcriptional level by deacetylation of FOxO1,a downstream molecule of Sirt1.Sirtl/Foxo1/APN pathway plays an important role in the process of insulin secretion.Objectives:To observe the effect of Jiaotai pill combined with swimming on(3 cell function based on Sirt1/Foxo1/APN pathway in type 2 diabetic mice.Methods:Eighty-four SPF male C57BL/6 mice were randomly divided into 2 groups,including control group(n=14)and T2DM model group(n=70).Mice in control group were given a normal diet,while in the model group a high-fat diet was introduced.After 4 weeks,mice in model group received intraperitoneal injection of streptozotocin(40mg/kg).Two weeks later,the mice which fasting blood glucose over 11.1mmol/l were confirmed as T2DM model.Then,mice in model group were randomly divided into 5 groups:control group(n=12);metformin group(n=12),swimming group(n=13),Jiaotai pill group(n=12),and Jiaotai pill+swimming group(combination group,n=12).Saline,metformin,and Jiaotai pill were given by lavage in each group.Mice in swimming group swam 5 days a week,30 minutes each time,and it lasted 4 weeks.Fasting blood glucose,insulin,blood lipid and adiponectin levels were detected before and after intervention.At the end of the intervention,intraperitoneal glucose tolerance test(IPGTT)and insulin release test(IRT)were performed to detect blood glucose and insulin levels,then HOMA-β index and early-phase insulin secretion evaluation indicators(A130/AG30 values)were calculated.After the mice were executed,the pathological changes of pancreatic islet were observed by immunohistochemistry,and the expressions of Sirtl and FoxO1 protein in pancreatic tissue were detected by Western blot.Results:1.The success rate of model induced by high fat diet and intraperitoneal injection of STZ is 87.14%in C57BL/6 mice.2.In T2DM mice,the fasting blood glucose and cholesterol increased(p<0.01),while the fasting insulin,HOMA-3(p<0.05)and adiponectin(p<0.01)decreased,as compared with the control group.3.After the intervention,the liver function,cholesterol and triglyceride in each group were not significantly changed.The level of adiponectin in the combination group was significantly higher than that of other groups(p<0.05).4.In diabetic group,the area under curve of blood glucose was significantly higher than that in control groups,while reduced significantly after the treatment of Jiaotai pill+swimming(p<0.05).5.The area under curve of insulin in diabetic group was significantly lower than that in control groups,whereas it increased significantly after the combination treatment(p<0.05).6.HOMA-β and△130/△G30 values in the control group were significantly higher than those in other groups(p<0.05).HOMA-β values in the combination group were higher than in other diabetic groups after treatment(p<0.05).7.Compared with the diabetes group,the pancreatic islet lesions in combination group were lighter,and the size and cell number of the islets increased.Also,the cell arrangement in the island was more regular in the combination group.Whereas,in other diabetes groups(metformin group,exercise group,and Jiaotai pill group),the changes were not significant.8.Sirtl expression was increased and FoxO1 expression was decreased in all intervention groups compared with diabetic group,with the expression of Sirl and FoxO1 in the combination group changed more significantly among diabetic mice(p<0.01).Conclusions:1.Jiaotai pill combined with swimming can effectively reduce blood glucose,promote insulin secretion,and β cell function in T2DM mice.2.The treatment of Jiaotai pill with swimming may protect 3 cell function through Sirt1/FoxO1/APN pathway. |
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