ABSTRACT
Objective Recent studies have shown that inflammatory cytokines are involved in the occurrence and development of diabetes mellitus .The article aimed to investigate the effects of anti-inflammatory drug--diacerein on hepatic PPAR-γand GLUT-2 protein expression and its role in the regulation of glucose and lipid metabolism in rats with type 2 diabetes mellitus ( T2DM) . Methods 55 male SD rats were randomly divided into 4 groups:normal control group (n=10), T2DM group (n=15), pioglitazone intervention group(n=15), and diacerein treatment group(n=15) .Rats in normal control group were fed with normal diet , the other 3 groups were fed with high fat diet .At the end of 8th experi-ment week, rats in 3 groups fed with high fat diet were treated with intraperitoneal injection of 30mg/kg streptozotocin ( STZ) solution, while rats in normal control group were injected with the same volume of sterile sodium citrate solution .At the end of 10th week, OGTT modeling rats were screened .Rats in pioglitazone intervention group were treated with 10 mg/kg pioglitazone by intragastric administra-tion, rats in diacerein group was treated with 50mg/kg diacerein by intragastric administration , and rats in normal control group and T2DM group were given the same volume of normal saline .The intervention lasted 4 weeks.At the end of 8th, 10th and 14th week, the blood examination of glycolipid , FINS, IL-1βand liver function indexes was done on fasting rats .Fourteenth weeks later , after getting blood samples , all rats were sacrificed and liver tissues were isolated .Western blot was applied in the detection of PPAR γand immu-nohistochemistry was applied to detect GLUT-2 protein in livers. Results At the end of 8th week, the FBG level in pioglitazone in-tervention group increased compared with normal control group ( P0 .05) show-ing higher levels compared with T 2DM group ( P<0.01).At 14th weekend, the GLUT-2 expression levels in normal control group (0.209±0.023), pioglitazone intervention group (0.226±0.017) and diacerein treatment group (0.232±0.012) were higher than that of T2DM group (0.173±0.009,P<0.01);and the GLUT-2 expression levels in pioglitazone intervention group and diacerein treatment group were higher than that of normal control group (P<0.05).The expression level of liver PPAR-γwas in positive correlation with those of GLUT-2 protein, HDL-C, FINS, ISI ( r=0.815, 0.780, 0.747, P<0.01) and in negative correlation with those of FBG , HbA1c, TC, TG, AST, ALT, IL-1β(r=-0.465,-5.716,-0.615,-0.675,-0.617,-0.521,-4.827, P<0.05). Conclusion Diacerein can enhance liver PPAR-γand GLUT-2 expression levels and reduce the levels of IL-1β, HbA1c and blood lipid, thus im-prove insulin resistance in T 2DM rats.
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.
ABSTRACT
Objective To construct PPAR?and PPAR?response element (PPRE)-controlled luciferase expression vectors,and to determine whether the traditional Chinese medicine emodin activates PPAR?and improves the glucose uptake by HepG2 hepatocytes.Methods (1) PPAR?and PPRE luciferase expression vectors were constructed and were applied to screen more than 20 ingredients of the traditional Chinese medicine. (2) HepG2 cells were incubated with emodin which can activate PPAR?and PPRE luciferase activity,and the PPAR?mRNA expression level was evaluated by RT-PCR/Southern blot.(3) PPAR?and glucose transporter 2 (Glut2) proteins were determined by Western blot analysis in HepG2 cells treated with emodin.(4) The glucose uptake rate was measured using 2-deoxy-[~3H]-D-glucose in HepG2 cells after treatment with emodin.Results (1) Emodin stimulated luciferase activity controlled by PPRE in dose-dependent manner at concentrations of 0.04 to 180?mol/L in COS-7 cells.The highest value was about 4 folds of control in the cells treated with 90?mol/L emodin (P