An Experimental Study On The Action Mechanism Of Improvement Of Glucose Metabolism Of Diabetic Rats By Exercise Therapy

Partâ… Objective This study was designed to examine the mechanism of beneficaleffects of exercise on streptozotocin-induced diabetic rats by studyinginsulin binding in brain, liver and skeletal muscle.Method SD rats were divided into three groups as exercised diabeticgroup, non-exercised diabetic group and normal control group. The rats inexercised diabetic group were submitted to 6 weeks swimming. Then theblood glucose,serum insulin and Binding Capacity were detected.Result After 6 weeks swimming training, compared with non-exerciseddiabetic rats, blood glucose in exercised diabetic rats decreased from36.95mmolg/L to 26.35mmol/L (P＜0.05), insulin increased from 8.19μu/mLto 9.49μu/mL(P＜0.05), C-peptide increased from 0.217ng/mL to 267ng/mL(P＜0.05), the volume of water drunk decreased from 702ml/d. kgBW to 520ml/d. kgBW (P＜0.05), body weight increased from 0.188g/d to0.78g/d(P＜0.01). in skeletal muscle cell membrane from normal rats, BmaxandNSB were 22.2% and 77.8% respectively; from diabetic rats, were 12.6%and 87.4%; from exercised diabetic rats, were 13.4% and 86.8%(comparedwith non-exercised diabetic rats P＜0.001). in liver cell membrane fromnormal rats, NSB and Bmax were 11.27% and 88.73% respectively; fromdiabetic rats, were 8.17% and 91.82%; from exercised diabetic rats, were19.93% and 80.07%(compared with non-exercised diabetic rats P＜0.001). inliver cell membrane from rats, KD₁, BC₁ for high affinity receptor sitesand KD₂, BC₂ for low affinity receptor sites 0.027nMol, 2.09pMol/μgprotein, 2.06nMol,21.5pMol/μg protein respectively; from diabetic rats,they were 0.023nMol,3.16pMol/μg protein,4.88nMol,30.8pMol/μg protein;from exercised diabetic rats, were 0.008nMol,0.64pMol/μg protein,4.86nMol,11.6pMol/μg protein (compared with non-exercised diabetic ratsP＜0.001,P＞0.05,P＜0.001,P＜0.01 respectively), we found that Bmax (maximum binding), NSB(non-specific binding), KD(Dissociation constant) andBC(Binding Capacity) for both high- and low-affinity sites of insulinreceptor did not significantly differ in brain cell membrane from normal,non-exercised and exercised diabetic rats(P＞0.05).Conclusion The results of this study indicate that exercise, in certainextent, can reduce the abnormality of insulin receptor in peripheraltissue of diabetic rats, improve glucose metabolism and might be able toenhance insulin secretion, but exercise has no effect on insulin receptorsin brain.Partâ…¡Objective To investigate the effect of exercise on the gene transcrip-tion and protein expression and the translocation of GLUT4 in the skeletalmuscle cell.Method Experimental rats were randomized into four groups: normalcontrol group, normal exercise group, streptozotocin-induced diabeticcontrol group and streptozotocin-induced diabetic exercise group, andeach group has six rats. After the rats in exercise groups were submittedto swim for 6 weeks, the skeletal muscle plasma membranes and theintracellular membranes were prepared and separated, the GLUT4 proteinwas detected by Western blot analysis and the GLUT4mRNA was detected byNorthern blot analysis.Result There was weak gene expression of GULT4 in diabetic rats, and dotblot revealed that the GLUT4 mRNA decrease 54.9% in skeletal muscle cellscompared with the normal control. Western blot analysis showed thatintracellular membranes GLUT4 protein of diabetic rats skeletal muscledecreased by 24.1%(P＜0.01) and plasma membranes GLUT4 protein decreasedby 48.1% (P＜0.01)as compared with the control rats. After 6 weeks ofexercise training, the plasma glucose level of diabetic exercise ratsdecreased form (18.5±1.9) mmol/L to (14.0±3.3) mmol/L (P＜0.01). Plasmamembranes GLUT4 protein of diabetic exercise rats increased 108.7%(P＜0.01) and intracellular membranes GLUT4 protein did not change ascompared with the diabetic rats. Conclusion Chronic hyperglycemia may inhibit the gene expression ofGLUT4 in diabetic rats which resulted that the level of GLUT4 protein indiabetic rats skeletal muscle cell decreased, and the level in the plasmamembrane decreased more than that in intracellular membranes, and thismay be one of the causes of hyperglycemia of diabetes. Exercise trainingcan improve the impaired GLUT4 expression in diabetic rats, which maycontribute to the mechanisms of enhanced insulin sensitivity anddecreased hyperglycemia in diabetes mellitus. Exercise training canameliorate translocation of GLUT4 and raise the amount of GLUT4 proteinin plasma membranes in diabetic rats, which may increase the utilizationof glucose in skeletal muscle and decrease hyperglycemia of diabetes.Partâ…¢Objective To observe the effect of exercise on protein expression andactivation of PKB/Akt, ERK1/2 and AMPK in normal and type 2 diabetic rats.Method A primary diabetic animal model namely OLETF rats were taken astype 2 diabetic group, divided into OLETF control group and OLETF exercisegroup; Age-matched non-diabetic LETO rats were taken as control group,divided into LETO control group and LETO exercise group. Each group hasfive rats. The exercise group were submitted into a bout of swimming forthree hours, then the protein expression and phosphorylation of PKB/Akt,ERK1/2 and AMPKαin soleus and extensor digitorum longus were measuredand compared by Western blot.Result Compared with that of LETO rats, the protein expression andphosphorylation of PKB/Akt, AMPKαin soleus and extensor digitorumlongus of OLETF rats showed no significant decrease. The phosphorylationof ERK2 was decreased with 37.6% and 27.8%respectively(P＜0.05). Aftera bout of exercise, there was no significant difference in the proteinexpression of PKB/Akt, ERK1/2 and AMPKαbetween exercise group and controlgroup, yet phosphorylated PKB/Akt and ERK1/2 increased in exercise groupcompared with control rats both in OLETF and LETO rats (P＜0.05); At thesame time, phosphorylated AMPKαincreases in extensor digitorum longusbut not in soleus in both OLETF and LETO rats. Conclusion Exercise may promotes the activation of PKB/Akt and ERK1/2 butnot their protein expression in soleus and extensor digitorum longus ofboth normal and type 2 diabetic rats. It suggests that PKB/Akt and ERK1/2are probably involved in the intracellular mechanisms by which exercisestimulates the glucose uptake in skeletal muscle of normal and type 2diabetic rats. AMPK is probably involved in the signal transductioncascade induced by exercise in fast extensor digitorum longus and itsresponseness to exercise maybe is related to the type of muscle fiber.Partâ…£Objective To investigate the role of leptin in insulin resistance and themechanism of exercise improving insulin resistance, We carry out theanimal experiment to find theeffect of exercise on the plasma level ofleptin and the expression of obese gene in spantenously diabetic rats.Method 40 OLETF rat and 15 LETO rat are randomized into six groups:non-exercise chow-fed OLETF group, exercise chow-fed OLETF group,non-exercise high-fat diet OLETF group, exercise high-fat diet OLETFgroup, non-exercise chow-fed LETO group and exercise chow-fed LETO group.After 9 weeks of different chows and swimming training, the plasmaconcentration of glucose and TG and TC and apodipose-proteins are measuredby means of auto-biochemistry instrument, the plasma concentration ofglucose and lipid is measured by auto-biochemistry instrument.Result The circulating concentration of TG in two non-exercised groupsof OLETF rats are higher than that of non-exercised LETO groupsignificantly (P＜0.05), the average serum levels of TC and LDL in twonon-exercised groups are higher than those of that of non-exercised LETOgroup respectively (P＜0.05), the serum levels of TC and LDL in the threeexercise groups are significantly lower than those of their non-exercisecontrol groups respectively (P＜0.05); the circulating concentration ofTG in the OLETF and LETO exercise groups feed by standard chow decreasedsignificantly. OGTT demonstrate that the incidence rates of IGT(impairedglucose torlence, IGT)) in OLETF rat non-exercised groups are higher than that of LETO rat non-exercised group, and the incidence rates ofIGT(impaired glucose torlence, IGT) in OLETF rat exercised groups arelower than those of OLETF rat non-exercised groups (P＜0.05). The plasmalevel of Leptin in exercised OLETF groups are significantly higher thannon-exercised OLETF groups (P＜0.01), the difference of the plasma levelof Leptin between non-exercised and exercised LETO group is notsignificant in statistics. The level of oh mRNA expression in exercisedOLETF groups are significantly lower than non-exercise OLETF groups(P＜0.01), the difference of The level of ob mRNA expression betweennon-exercised and exercised LETO group is not significant in statistics.Conclusion The disorders of glucose and lipid metabolism in OLETF ratsare gradually caused by the surplus intake of food mainly due to the genemutation, subsequently the leptin resistance occurred in OLETF rats makethe disorder worse. Exercise can improve insulin resistance by impovingleptin resistance in OLETF rats.