Insulin Resistance And Mechanism Of Hepatic KKAy Mice Treated With Adjuvant Hypoglycemic Granules Combined With Pioglitazone

[Objective]To observe the effect of adjuvant hypoglycemic granule(FT-5)combined with pioglitazone on glucose and lipid metabolism and insulin resistance in KKAy mice,to provide the scientific basis for the combination of Chinese and western medicine and to provide guidance for clinical care.[Methods]6-8 weeks old female KKAy mice with initial weight of 30-35 grams selected out of 100 mice were randomly divided into 7 groups of 10.C57BL/6J mice were fed with regular granular feed with full nutrition.KKAy mice,having met the following criteria after 4 weeks of high fat feeding,were randomly divided into 7 groups of 10 each:blood glucose>180 mg/dL,serum triglyceride>200 mg/dL,serum total cholesterol>150 mg/dL,and body weight between 45-55 g.In order to minimize the variance between the groups,the mice are randomly divided based on blood glucose,serum triglycride level,total cholesterol level,body weight and percentage point of blood glucose drop after injecting 0.4 IU/kg Insulin.Group 1,control group(Con),was given daily oral administration of equal volume of double-distilled water(ddH20);Group 2,high dose group(H),was given daily FT-5 of 2.0 g/kg body weight;Group 3,Concomitant drug group(P + FT-5),was given daily a mixed solution of FT-5 of 2.0 g/kg and pioglitazone of 20 mg/kg;Group 4,positive drug group(PIO),was given daily administration of pioglitazone solution of 20 mg/kg;Group 5,normal Control group(Nor),was given an equal volume of ddH20.RESULTS:Pioglitazone(20mg/kg)treatment remarkably reversed FBG,FINS,and impaired glucose tolerance.However,it significantly increased body weight,plasma TC levels,and liver TC and TG levels.FT-5 group(2g/kg)had no statistically significant decrease in plasma glucose.However,it reduced blood fasting TG levels and improved the fatty livers of KKAy mice.Mice treated with pioglitazone+FT-5 not only demonstrated an enhanced effect of pioglitazone’s insulin resistance effect.but also an ameliorated side effect of increased steatosis.Combination therapy not only limited the BW of KKAy below their baseline levels,but also accelerated fatty acid oxidation in liver.Additionally,pioglitazone administration markedly decreased the phosphorylationphosphoinositide AMPK level,while FT-5 and FT-5+pioglitazone did not change it.However,FT-5 further decreased liver IRS-1Ser307 level.CONCLUSION:Even though,FT-5 was not able to improve insulin resistance,it decreased plasma TG and alleviated pioglitazone aggravating steatohepatitis in KKAy mice,which might be associated with its ability to activate the adiponectin/AMPK pathway.