| Objective:Through 8-week high-fat diet to establish insulin resistance model in rats, then after a period of 4 weeks of hypoxia and exercise intervention to observe the effects of hypoxia and exercise on insulin resistance and lipid metabolism in rats,and then to explore the role of caveolins in insulin resistance.Methods:Forty-six five-week old male Sprague-Dawley(SD) rats were randomly divided into control group and high-fat-diet group, through fasting blood glucose, fasting insulin levels to the degree of insulin resistance(HOMA-IR) and insulin sensitivity(ISI),and glucose tolerance to determine whether the model is success.Rats with insulin resistance were randomly divided into four groups: normoxic control(NC), normoxic exercise(NE), hypoxic control(HC) and hypoxic exercise(HE). After four-week hypoxia and exercise intervention, rats abdominal aorta blood was measured to test serum triglyceride(TG), total cholesterol(TC), high-density lipoprotein(HDL-C), low-density lipoprotein(LDL-C) and free fatty acid(FFA) levels, immunofluorescence to observe the distribution of GLUT4 in rat soleus,and Western Blot to determine the protein expression of GLUT4,Caveolin-1 and Caveolin-3 of soleus.Results:(1)After 8-weeks high-fat diet, the rats showed insulin resistance:body weight increased significantly(P<0.01); FPG level has no significant changes, but the levels of FINS and HOMA-IR were significantly increased(P<0.01), ISI was significantly decreased(P<0.01); Glucose tolerance was serious damaged.(2)After 4 weeks of hypoxia and exercise intervention,body weight of group NE(P<0.01), HC(P<0.05) and HE(P>0.05) was significantly decreased;Exercise alone significantly decreased the level of FINS,FPG and HOMA-IR(P<0.01), ISI also increased(P<0.01); Hypoxia alone had no significant effect on FPG level(P>0.05),but FINS level and HOMA-IR were significantly lower(P<0.01) and ISI increased significantly(P<0.05); Hypoxia and exercise shows significantly effects on the level of FINS(P<0.01), FPG(P<0.05),HOMA-IR(P<0.01) and ISI(P<0.05);the damage degree of glucose tolerance of group NE,HC and HE were significantly erased.(3)Compared with control group, serum TG(P<0.05), TC(P<0.01), LDL-C(P<0.05) levels were significantly increased in NC group;Compared with NC group,serum TG, HDL-C and FFA levels were significantly decreased in group NE(P<0.01), HC(P<0.05) and HE(P<0.01);Serum TC level in NE group was significantly lower than that in NC group,but no significant changes were found in HC and NE groups;There were no significant change of serum LDL-C level in all the three groups(P>0.05).(4)Compared with control group, the fluorescence intensity of NC group was significantly decreased(P<0.05). The distribution of GLUT4 on soleus cell membrane in NE group and HE group was significantly higher than that in group NC,and the fluorescence intensity showed significantly difference(P<0.01).The distribution of GLUT4 in HC group was slightly increased(P>0.05).(4)The contents of protein GLUT4(including membrane parts), Caveolin-1 and Caveolin-3 in control group were lower than that in NC group, but not statistically significant(P>0.05);Compared with the NC group, GLUT4 total protein and membrane protein expression were increased in NE(P<0.05), HE(P<0.01);Caveolin-1 and Caveolin-3 expression in NE, HC and HE were all increased, but only the HE group had significant difference(P<0.05).Conclusions: Hypoxia exercise can effectively improve the insulin resistance induced by obesity and blood lipid metabolism, the effect of simple exercise is better than that of hypoxia, the improvement of insulin sensitivity in hypoxia with exercise sees a better trend; The effect of hypoxia on generation of GLUT4 and its distribution in skeletal muscle cells is not significant, but the effect of simple exercise is more obvious;The result that hypoxic exercise improve insulin sensitivity may be associated with the content of caveolin-3 increasing, the mechanism needs further study. |
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