Effects Of High Intensity Interval Training On Insulin Resistance And Learning/Memory Function In Diabetic Rats

Research objective:The number of diabetic patient is gradually increasing worldwide and studies have revealed that diabetes can increase the risk of cognitive dysfunction.Exercise is one of the important interventions for diabetes,which can efficiently regulate the level of blood glucose.Meanwhile,exercise can also protect neuronal plasticity and improve cognitive function.HIIT is a kind of interval exercise with high intensity and short duration and has been widely recommended in the prevention and treatment of diabetes because of significant effect on blood glucose control.However,the effect of HIIT on diabetes cognitive function and its related mechanisms are still unclear.Therefore,in this study,the type 2diabetic rats were used to investigate the effect of 8-week HIIT on the insulin resistance and the spatial learning and memory function,then analyze the possible biological mechanisms to provide experiment evidence of exercise improving diabetes cognitive impairment.Research method:Male Wistar rats（body weight:160～180g）were randomly divided into control group（CG,n=8）and diabetic model group（DMG,n=32）after one week of adaptive feeding.Diabetic rat model replication:4-week high fat diet feeding with a low dose of streptozotocin intraperitoneal injection（30 mg/kg）.High fat feed formula:60%standard laboratory feed,18%egg yolk powder,16%white sugar,5%lard and 1%sodium cholate.The successful criteria for the diabetic model replication:fasting blood glucose>11.1 mmol/L after 3 and 7 days of streptozotocin injection.Then the diabetic rats were randomly divided into diabetic control group（DG,n=12）and diabetic exercise intervention group（DEG,n=12）.DEG rats received the 5 times/week HIIT treadmill exercise intervention for 8 weeks.The HIIT intervention program:warm-up for 5 to 10 min,4 times 85%～95%VO_2max intensity exercise for 7 min（speed 25 m/min）followed by 50%～60%VO_2max intensity exercise for 3min（speed was 15 m/min）]and finally cool down for 5 to 10 min.Body weight and fasting blood glucose were monitored and recorded weekly during the intervention.After the intervention,the Morris water maze was used to detect the spatial learning and memory ability of each group.After the Morris water maze experiment,serum and hippocampal tissue samples from each group of rats were collected.The serum triglyceride,total cholesterol,high-density lipoprotein and low-density lipoprotein were detected by enzymatic method;The serum insulin and insulin-like growth factor 1 levels were detected by enzyme-linked immunosorbent assay;The insulin resistance index（HOMA-IR）and isletβ-cell function index（HOMA-β）were calculated by the fasting blood glucose and insulin;HE staining was used to observe the morphology of hippocampal CA1 neurons;immunohistochemical staining was used to observe and calculate theβamyloid deposition of hippocampal CA1 region;The hippocampal insulin receptor,insulin-like growth factor-1 receptor,insulin receptor substrate1 and its 307 serine site phosphorylation and insulin receptor substrate 2 and its 731 serine site phosphorylation were detected separately by Western Blot.Finally,the data from Water maze were compared by repeated measures analysis of variance,and the other data were compared by one-way analysis of variance.P<0.05 was considered to be significant difference and P<0.01 was considered to be very significant difference.Research result:（1）Compared with rats in CG,the serum FBG,TG,TC,LDL and HOMA-IR of rats in DG increased,the serum insulin,IGF-1,HDL and HOMA-βdecreased（P<0.01 or P<0.05）.However,after HIIT intervention,compared with rats in DG,the serum FBG,TG,TC,LDL and HOMA-IR of rats in DEG decreased,the serum HDL and HOMA-βlevels increased（P<0.01 or P<0.05）.（2）Compared with rats in CG,the number of platform crossings,the time to stay in the target quadrant and the ratio of the distance in the target quadrant in the space exploration experiment of Morris water maze of rats in DG decreased（P<0.01）.However,after HIIT intervention,compared with rats in DG,the number of platform crossings,the time to stay in the target quadrant and the ratio of the distance of rats in DEG increased（P<0.01 or P<0.05）.But,in the 5-day navigational experiment,there was no significant difference in escape latency between any groups（P>0.05）.（3）Compared with rats in CG,the HE results of hippocampal CA1 region of rats in DG showed that the neurons were loosely arranged,the nucleus was pyknosis and the staining deepened.However,after HIIT intervention,compared with rats in DG,the HE results of hippocampal CA1 region of rats in DEG showed that the neurons arranged neatly with clear nuclei and abundant cytoplasm.Meanwhile,the neuronal morphology and structure tended to be normal.（4）Compared with rats in CG,the expression of p-IRS-1,p-IRS-2 and Aβin hippocampus of rats in DG was up-regulated and the expression of IGF-1R was down-regulated（P<0.01）.Meanwhile,the expression of insulin receptor decreased but there was no significant difference（P>0.05）.However,after HIIT intervention,compared with rats in DG,the expression of p-IRS-1 and p-IRS-2 in hippocampus of rats in DEG was down-regulated and the expression of IGF-1R was up-regulated（P<0.01）.But HIIT had no significant effect on the Aβdeposition and IR expression（P>0.05）.Research conclusion:（1）Eight-week HIIT intervention can reduce elevated blood glucose and lipid levels,and improve insulin resistance in T2DM rats.（2）Eight-week HIIT intervention can improve the impaired spatial memory function of T2DM rats,and the underlying mechanism may be related to the down-regulation of p-IRS-1and p-IRS-2 expression of hippocampus insulin receptor signnalling pathway,the the improvement of central insulin resistance and the improvement of impaired hippocampus neuronal structure.