Rhein Improves The Hyperglycemia, Insulin Sensitivity Of Diabetic Rats And Increases The Expressions Of PPARγ, GLUT-2 In Hepatic Tissue

Objective In this study,we aimed to investigate the effects of rehin on the insulin sensitivity in diabetic rats induced by injecting low dose STZ after high fat feeding for 5 weeks,and the possible mechanisms.Methods(1)Fifty-five male wistar rats were divided randomly into normal control group(NC,n=15)and diabetes group(DM,n=40),the NC group was fed with regular chow,DM group was fed with high fat diet.The rats of DM group were injected of STZ 30 mg/kg once five weeks later,the fasting blood glucose (FBG)was detected one week later,the rat whose FBG was higher than 11.1mmol/l and had the symptoms of polydipsia and polyuria were chosen as the diabetic rat.The total thirty of diabetic rats were randomly devided into two subgroups,diabetic control group(DM-C)and diabetic group treated with rhein (DM-T).The DM-T rats started intragastric administration of rhein(100 mg·kg-1·d-1)and DM-C rats were given equal doses of solvent.(2)All rats were sacrificed eleven weeks later,the blood sample was collected;the body weight, FBG,glycosylated hemoglobin(HbA₁c),glycosylated serum protein(GSP), triglyceride(TG),total cholesterol(TC)and Fasting insulin concentration(FIN) were examined.The insulin sensitive index(ISI)and Homa insulin resistant index (Homa-IR)were calculated.(3)The PPARγ,and GLUT-2 expression in hepatic tissue were detected by immunohistochemistry and Western-blot.Results(1)After one week of injection with STZ,the FBG of DM group was higher than NC group significantly(15.48±4.47 vs 5.93±0.58 mmol/l,P＜0. 01).The FBG was detected regularly during the animal feeding,the DM-C rats were markedly higher than NC rats.(2)At the end of 17^thweek,compared with NC rats,the FBG(22.574±3.23 vs 7.114±1.44 mmol/l,P＜0.01),HbA₁c(12.494±1.96 vs 8.36±0.84%,P＜0.01),TG(0.89±0.29 vs 0.58±0.17 mmol/l,P＜0.01),GSP (57.29±4.14 vs 13.43±2.7,P＜0.01)and TNF-α(1.365±0.133 vs 1.233±0.159 ng/ml,P＜0.05)of DM-C rats were significantly higher than NC rats,the liver weight index was higher than that in NC rats(0.032±0.004 vs 0.024±0.002, P＜0.01).Besides of these,the ISI decreased(-5.46±0.61 vs -4.81±0.75,P＜0.05), the Homa-IR elevated significantly[8.26(7.67,9.62)vs 7.07±4.98,P＜0.05].The expression of PPARγ[11131.7(5723.1,18979.4)vs 48782.1(21576.7,108829.5), P＜0.01]and GLUT-2(0.98±0.35 vs 1.29±0.27,P＜0.05)of DM-C rats,compared with NC rats,decreased markedly.(3)In the 8^thweek of treatment,the FBG in DM-T rats were lower than DM-C rats significantly(13.59±4.52 vs 17.74±3.33 mmol/l,P＜0.05).At the end of 17^thweek,compared with DM-C rats,the DM-T rats had lower body weight(384.2±34.26 vs 428±39.94 g,P＜0.01),FBG (15.94±3.16 vs 22.57±3.23 mmol/l,P＜0.01),HbA₁c(10.51±1.74 vs 12.49±1.96%, P＜0.05)and GSP(47.31±6.09 vs 57.29±4.14μmol/l,P＜0.01).The ISI of DM-T rats was higher(-4.97+0.29 vs -5.46±0.61,P＜0.05)and the Homa-IR was lower [6.1(5.29,7.22)vs 8.26(7.67,9.62),P＜0.05]than DM-C rats.The expression of PPARγ,[35156.3(24554.3,86660.9)vs 11131.7(5723.1,18979.4),P＜0.01]and GLUT-2(1.55±0.55 vs 0.98±0.35,P＜0.05)of DM-T rats,compared with DM-C rats,were up-regulated markedly.Conclusion Rehin decreased FBG,HbA₁c and GSP of DM-C rats and improved the insulin sensitivity.The mechanisms might be related to the up-regulated expression of PPARγ,and its downstream gene GLUT-2 in hepatic tissue.