Rhein improves fasting blood glucose, insulin sensitivity of diabetic rats and increases expression levels of PPARγ, GLUT-2 in hepatic tissue / 中华内分泌代谢杂志

ABSTRACT

Objective To investigate the effects of rhein on insulin sensitivity of diabetic rats induced by high fat feeding and low dose streptozotocin (STZ), and the possible mechanisms. Methods (1) Fifty-five Wistar rats were randomly divided into normal control group (NC,n=15) and diabetes group (DM, n=40). The NC rats were fed with regular chow and DM rats were fed with high fat diet. Five weeks later, the DM rats were injected with STZ 30 mg/kg once. The 30 diabetic rats were randomly divided into two subgroups, diabetic control group (DM-C) and diabetic group treated with rhein (DM-T). DM-T rats received intragastric administration of rhein and DM-C rats were given equal doses of solvent. All rats were sacrificed eleven weeks later, the blood sample was collected. The body weight, fasting blood glucose (FBG), HbA1C, triglycerides (TG), tolal cholesterol (TC), glycosylated serum protein (GSP) and Fasting insulin (FINS) concentrations were examined.The insulin sensitive index (ISI) and homeostasis model assessment for insulin resistance (HOMA-IR) werecalculated. (2) The PPART and GLUT-2 expression in hepatic tissue were detected by immunohistoehemistry and Western-blot. Results At the end of experiment the FBG [(22.57±3.23 vs 7.11±1.44) mmol/L,P<0.01],HbA1C[(12.49±1.96 vs 8.36±0.84)%, P<0.01], TG [(0.89±0.29 vs 0.58±0.17)nunoL/L,P<0.01],GSP [(57.29±4.14 vs 13.43±2.70)μmoL/L, P<0.01] and tumor necrosis factor-α [TNF-α,(1.365±0.133 vs 1.233±0.159) μg/L, P<0.05] and the liver weight index (0.032±0.004 vs 0.024±0.002, P<0.01) in DM-C rats were higher than those in NC rats. Besides, the ISI of DM-C rats decreased [In(ISI),-5.46±0.61 vs -4.81±0.75, P<0.05] and HOMA-IR elevated [In(HOMA-IR),2.34±0.64 vs 1.70±0.78,P<0.05]. The expression of PPARγ [11 131.7(5 723.1-18 979.4) vs 48 782.1(21 576.7-108 829.5), P<0.01] and GLUT-2 (0.98±0.35 vs 1.29±0.27, P<0.05) of DM-C rats decreased markedly compared with NC rats. Compared with DM-C rats, FBG [(15.94±3.16) mmol/L], HbA1C[(10.51±1.74)%], GSP[(47-31±6.09) μmol/L] in DM-T and the In (HOMA-IR), (1.86±0.30) rats decreased (P<0.05 or P<0.01), and In (ISI), of DM-T rats increased (-4.97±0.29, P<0.05). The expressions of PPARγ [35 156.3(24 554.3-86 660.9)] and GLUT-2 (1.55±0.55) of DM-T rats were up-regulated markedly compared with DM-C rats (P<0.05 or P<0.01). Conclusion Rhein decreased FBG, HbA1C and GSP, and improved the insulin sensitivity in diabetic rats, which might be related to the up-regulated expressions of PPARγ and GLUT-2 in hepatic tissue.