الفهرس 
ACKNOWLEDGEMENTOnly 14 pages are availabe for public view
 |  | from | 200 |  |  |
| | | from | 200 | | |
Abstract
The present study was aimed to investigate the action of various antidiabetic drugs (Metformin, Pioglitazone and Sitagliptin) on insulin resistance, some biochemical parameters and levels of pro-inflammatory cytokines (TNF-α, IL-6, High sensitivity CRP), which can contribute in diabetic vascular complications in rats fed HFD and low dose of Streptozotocin (STZ) as a model for Type II Diabetes (T2DM). Ninety Sprague-Dawley (SD) male rats were included in this study, from which 15 were randomly selected as the normal control group (group A) and the remaining 75 were considered as T2DM model group. group A was fed with commercial balanced diets and the T2DM model group, with high fat diets (58% fat, 25% protein and 17% carbohydrate, as a percentage of total kcal). After 6-week feeding, the T2DM model group was injected i.p. with low dose of STZ (25 mg kg b.w.) then randomly allocated into four groups according to the drug treatment, Diabetic (group B), Janumet (group C), Janumet plus Pioglitazone (group D), and Metformin plus Pioglitazone group (group E). After 4 and 8 weeks from beginning of drugs treatment, body weight, fasting blood glucose levels, fasting insulin levels, c-peptide, Glucagon level and HbA1c were measured as well as serum levels of pro-inflammatory cytokines (TNF-α, IL-6, hsCRP) and IgM and IgG were determined. Also serum lipid profile was estimated and HOMA IR calculated. Levels of serum Creatinine,Urea, SGPT, amylase and lipase as well as TSH were estimated for study the safety of drugs used on renal, hepatic, pancreatic and thyroid tissues respectively. All data were statistically analyzed. Diabetic rats were showing highly significant increase in plasma glucose level, HbA1c,C-Peptide, Total cholesterol (TC), Triacylglycerol (TAG), Low-density lipoproteins (LDL-c), insulin resistance (IR) with hyperinsulinemia as well as levels of TNF-α, IL-6, hsCRP and Thyroid stimulating hormone (TSH) were significantly elevated while High-density lipoprotein-cholesterol (HDL-c) and Amylase significant decrease. On the other hand, body weight was showed a different behavioral pattern, where it was detectably significant decrease in the end of experiment with significant hyperglucagonemia. While treated groups showed a significant improvement in blood levels of glucose, HbA1c, insulin, C-Peptide and Glucagon levels as well as Total cholesterol (TC), Triacylglycerol (TAG), Low-density lipoproteins (LDL-c), insulin resistance (IR) and levels of pro-inflammatory cytokines (TNF-α, IL-6, hsCRP) also lowered, beside serum Creatinine, Urea and SGPT levels in all treated groups not significant affected as
well as TSH, Lipase and Amylase levels. This study indicated that antidiabetic drugs used (Metformin, Pioglitazone and Sitagliptin) in a combination therapy were improved carbohydrates metabolism, insulin sensitivity and pro-inflammatory cytokines levels beside their safety on kidney, liver, pancreas and thyroid tissues.