RESUMO
BACKGROUND:Skeletal muscle insulin resistance is the key pathological link of type 2 diabetes.Static exercise can effectively improve skeletal muscle insulin resistance,but the mechanism remains unclear. OBJECTIVE:To explore the mechanism of static exercise on insulin resistance in the skeletal muscle of type 2 diabetic mice based on the phosphatidyl inositol 3-kinase(PI3K)/protein kinase B(AKT)/glucose transporter(GLUT4)signaling pathway. METHODS:After 1 week of adaptive feeding,7 out of 40 C57BL/6 mice were randomly selected as blank group and fed common diet,while the other mice were fed high-fat diet and taken to prepare type 2 diabetes models through the low-dose streptozotocin intraperitoneal injection.Twenty-four mice were successfully modeled and they were randomly divided into model group(n=8),metformin group(n=8)and static exercise group(n=8),which continued to be fed high-fat diet.The metformin group was given 200 mg/kg metformin dissolved in normal saline(2 ml/kg)by gavage,once a day,for 6 weeks.The static exercise group was given normal saline daily by gavage and carried out static exercise,30 minutes a day,6 days per week.The model group was given the same dose of normal saline daily by gavage without exercise intervention.After the intervention,the fasting blood glucose of each group was detected,the intraperitoneal glucose tolerance test was performed,and the area under the glycemic curve was calculated.Glycosylated hemoglobin,serum insulin,insulin resistance index were detected by ELISA.Total cholesterol,triglyceride,high-density lipoprotein,low-density lipoprotein were detected using biochemical methods.The mRNA expression levels of PI3K,AKT and GLUT4 in the gastrocnemius of mice were detected by real-time quantitative PCR.Morphological changes of the gastrocnemius were observed by hematoxylin-eosin staining,and the cross-sectional area of muscle fibers was calculated. RESULTS AND CONCLUSION:Compared with the blank group,fasting blood glucose,glycosylated hemoglobin,area under the glycemic curve,insulin resistance index,total cholesterol,triglyceride and low-density lipoprotein levels were significantly increased in the model group(P<0.01,P<0.05).Whereas,these indicators were significantly lower in the static exercise and metformin group than the model group(P<0.01,P<0.05).Compared with the blank group,serum insulin and high-density lipoprotein levels were significantly declined in the model group(P<0.01)and the mRNA expression of PI3K,AKT and GLUT4 in the gastrocnemius of mice were also significantly reduced(P<0.01).These indicators were significantly elevated in the metformin group and static exercise group compared with the blank group(P<0.01).Compared with the blank group,the muscle fibers in the model group were disordered,and the muscle cells atrophied and the muscle fiber gap widened.The cross-sectional area of muscle fibers was significantly decreased in the model group compared with the blank group(P<0.01).Compared with the model group,atrophy of the gastrocnemius fibers and muscle fiber space were improved in the static exercise group and the metformin group,and the cross-sectional area of muscle fiber was significantly increased in both groups(P<0.01).These findings indicate that static resistance training may promote glucose uptake and utilization by up-regulating the expression of PI3K,AKT and GLUT4 mRNA in skeletal muscle tissue,thereby improving the morphology and function of skeletal muscle tissue,alleviating insulin resistance and regulating glucose homeostasis.
RESUMO
OBJECTIVE：To study the effects of Purple frute scens leaves polysaccharides （PPLPs）on oxidative stress and PI3K/AKT/GLUT4 signaling pathway of pancreatic tissues in diabetes mellitus （DM）model mice. METHODS ：Totally 60 mice were given intraperitoneal injection of STZ （60 mg/kg）to induce DM model. The 40 successful modeling mice were randomly divided into model group ，metformin group （positive control ，200 mg/kg），PPLPs high-dose and low-dose groups （400，200 mg/kg），with 10 mice in each group. Another 10 healthy mice were selected as the normal group （normal saline ）. They were given relevant medicine intragastrically ，once a day ，for consecutive 28 days. During the experiment ，general information and body weight of mice were observed ；oral glucose tolerance （OGTT）test（determining FBG at 0，30，60，120 min after giving 40％ glucose solution ）was conducted. After last medication ，the changes of related blood glucose indexes （FBG，FINS，ISI，IRI）， blood lipid indexes （HDL-C，LDL-C，TC，TG）and oxidant stress indexes （MDA content and the activities of SOD ，CAT， GSH-Px）as well as the protein expressions of PI 3K，p-AKT and GLUT 4 in pancreatic tissue were determined. RESULTS ：During the experiment ，compared with normal group ，the mice were slow in action ，the feed consumption and water consumption increased，and body weight significantly increased in model group （P＜0.05）. 0，30，60，120 min after giving glucose ，the FBG content of mice were all increased significantly （P＜0.05）. After last medication ，the contents of FINS and HDL-C in serum as well as ISI ，the activities of SOD ，CAT and GSH-Px as well as the protein expressions of PI 3K，p-AKT and GLUT 4 in pancreatic tissue were all decreased significantly （P＜0.05）；the contents of FBG and LDL-C ，TC and TG in serum as well as IRI ， 疗。E-mail：sunguangping83@163.com MDA content in pancreatic tissue were all increased significantly（P＜0.05）. Compared with model group ，the general condition and OGTT of mice in each administration group was improved；the contents of FINS and HDL-C in serum as well as ISI ，the activities of SOD ，CAT and GSH-Px as well as the protein expressions of PI 3K，p-AKT and GLUT 4 in pancreatic tissue were all increased significantly （P＜0.05）；the contents of FBG，LDL-C，TC and TG in serum as well as IRI ，MDA content of pancreatic tissue were decreased significantly （P＜0.05）. CONCLUSIONS：PPLPs has anti-diabetic effects ，which are related to reducting oxidative stress level and promoting the activation of PI 3K/AKT/GLUT4 signaling pathway.