Effects Of Pioglitazone On The Renal And Inflammatory Factor Of Rat Models With Type 2 Diabetes

Objective To establish a rat model similar to human type 2 diabetes mellitus (T2DM)and to evaluate the insulin sensitivity using euglycemic hyperinsulinemic clamps technique.Methods SD rats(n=90) were randomized into control group(n=20) and high-fat diet (HF)group(n=70),the latter were fed with high-fat emulsion via gavage,the control group were treated with the same volume of normal sodium,routin animal feeds were available freely for both group.The body mass (BM)were measured weekly.At 5 months, The BM,systolic blood pressure (SBP),serum triglyeride (TG),fasting blood sugar (FBG),fasting insulin (FIns)were measured.Insulin sensitivity of 6 rats from each group were evaluated using euglycemic hyperinsulinemic clamps technique by observeing their glucose infusion rate(GIR).Streptozotocin(STZ,12mg/kg) and complete Freund's adjuvant (CFA,0.5ml/kg) were administered to the remain HF rats via intraperitoneal injecting,once a week,no more than 3 times.The rats whose random blood sugar > 11.1mol/L were diagnosised type 2 diabetes. Results①The BM,SBP,level of serum TG in HF group at 5 months were significantly higher than those in the control group(P <0.05).②FBG were increasing in the HF group but there was no significant difference compared with the control group,FIns and insulin sensitivity index(ISI) were significantly higher than those in the control group(P <0.05).③The HF group acquired significant lower GIR compared with the control group(P <0.05).④After treated with STZ and CFA, random blood sugar of 53 rats were higher than 11.1mol/L,accounted 85%of the total.Conclusion Intraperitoneal injecting low dose of STZ and CFA after long time of high-fat diet to rats may induced to type 2 diabetes similar to human. Objective To observe effects of pioglitazone on the renal and inflammatory factor of rat models with type 2 diabetes ,exploring possible partial mechanism.Methods Rats with type 2 diabetes were fed with high fat emulsion continually and boiled water,randomized into DM and PIO group according to the blood sugar and the body mass(BM), the PIO group were administed pioglitzone via gavage(10mg/kg.d), the DM group and normal control (NC)group were treated with the same volume of sodium carboxymethycellulose. After 6 weeks, BM,kidney hypertrophy index (kidney mass /body mass KM/BM ), urinary albumin(UAL),fasting blood glucose(FBG), glycosylated hemoglobin-A1c (HbA1c) ,serum C-reactive protein(CRP)and nitric oxide(NO)were measured and kidney samples were observed using light microscope and electron microscope respectively.Results①UAL in the DM and PIO groups was higher than that in the NC group before the treatment,but there was no significant difference; after the treatment, the UAL in the DM group was increasing, significantly higher than that in PIO and NC groups(P <0.05);UAL in the PIO group was significantly higher compared with the NC group and pretherapy(P <0.05), however the increasing extent was lower than that of the DM group(P <0.05).②The serum FBG,HbA1c in the DM and PIO groups were significantly higher compared with the NC group(P <0.05)and there was no significant difference between the two groups after the treatment.③The kidney hypertrophy index and the level of serum CRP in the DM group were significantly higher than those in the NC and PIO groups and there was no significant difference between the NC and PIO groups.④The level of serum NO in the DM and PIO groups were significantly lower than those in the NC group,there was no significant difference between the DM and PIO groups.⑤mesangial proliferation , glomerular basement membrane (GBM) thickening and glomcrulus hypertrophy existed in DM group,while slight chang existed in the PIO group.Conclusion①PIO decreases UAL and kidney hypertrophy index of the rats with type 2 diabetes.②PIO decreases the level of serum CRP .③6 weeks of administing PIO to rats has no significant effect on the level of serum FBG,HbA1c.④PIO mitigates the morphologic lesioning of kidney in the rats with T2DM.⑤Inhibiting inflammatory reaction may be one of the mechanism for renal procection of PIO,which is independent on the hypoglycemic activity.