The Study Of Mechanism On Abnormal Glucose Metabolism Induced By Statins Through Inhibiting Autophagy In Rats

Objective:Rats model of abnormal glucose metabolism induced by high dose atorvastatin calcium was established to investigate the effect of autophagy level on abnormal glucose metabolism in vivo.Methods:Sixteen healthy male Wistar rats were randomly divided into two groups: the control group(n = 8)and the atorvastatin calcium intervention group(n = 8).Rats in the atorvastatin calcium intervention group were given atorvastatin calcium(50 kg·kg-1·d-1)by intragastric administration and in the control group were given an equal amount of deionized water for 24 hours.Then an oral glucose tolerance test and measures of insulin release were performed.HOMA-?,HOMA-IR and HOMA-IS were calculated.The blood biochemical parameters were also examined.Western blot was used to detect the expression of autophagy associated proteins LC3-II and P62.Results:1.The weight and triglycerides of atorvastatin calcium intervention group were significantly lower than the the control group(P < 0.05).2.The oral glucose tolerance test showed that atorvastatin calcium treatment did not modify the fasting blood glucose level,but at 30 min[(9.54 ± 0.59)mmol/L vs(7.24 ± 1.45)mmol/L]?60 min[(8.90 ± 0.76)mmol/L vs(7.33 ± 1.47)mmol/L]?90 min[(7.88 ± 1.28)mmol/L vs(5.84 ± 0.81)mmol/L]?and 120 min[(6.87 ± 0.63)mmol/L vs(5.20 ± 0.56)mmol/L] after glucose intake,the blood glucose levels in the atorvastatin calcium intervention group were all significantly higher than those of the control group(P < 0.05).3.The serum insulin levels before [(4.08 ± 1.62)mmol/L vs(8.27 ± 4.19)mmol/L]? and 30 min[(4.99 ± 3.07)mmol/L vs(12.89 ± 4.83)mmol/L]?60 min[(4.75 ± 1.62)mmol/L vs(13.92 ± 5.2)mmol/L]?90 min[(4.59 ± 1.75)mmol/L vs(12.63 ± 3.36)mmol/L]?120 min[(3.68 ± 1.93)mmol/L vs(10.74 ± 3.35)mmol/L] after glucose intake,the serum insulin level of atorvastatin calcium intervention group were all significantly lower than those of the control group(P < 0.05).HOMA-? and HOMA-IR decreased significantly,while the HOMA-IS increased significantly in the atorvastatin calcium intervention group(all P < 0.05).4.No significant differences were found in the pathology of pancreas under an optical microscope between the two groups.5.The express level of autophagy associated protein LC3-II[(0.33 ± 0.02)vs(0.84 ± 0.04)] decreased significantly in atorvastatin calcium intervention group compared with the control group,while the P62[(0.20 ± 0.01)vs(0.28 ± 0.02)] increased significantly in atorvastatin calcium intervention group(all P < 0.05).Conclusions:1.The oral glucose tolerance test confirms that a rats model with abnormal glucose metabolism can be successfully established,which provides a possibility for future research.2.The mechanism of abnormal glucose metabolism induced by high dose atorvastatin calcium may be partly by inhibiting autophagy.