Comparative study between atorvastatin and losartan on high fat diet-induced type 2 diabetes mellitus in rats.
Obesity is often associated with chronic inflammatory state which contributes to the development of insulin resistance (IR) and type 2 diabetes mellitus (T2DM). This study investigated the effects of single and combined administration of atorvastatin (ATOR, lipid-lowering drug) and losartan (LOS, angiotensin receptor antagonist) on metabolic disorders and inflammatory status that are implicated in the development of T2DM with the use of pioglitazone (PIO) as a standard antidiabetic drug. T2DM was induced in male rats by high-fat diet (HFD) feeding for 16 weeks. Oral administrations of ATOR (10 mg/kg), LOS (20 mg/kg), PIO (3 mg/kg), their binary combinations, or vehicle were started in the last 4 weeks. Fasting serum glucose, oral glucose tolerance, fasting serum insulin, IR, serum lipid profile, serum TNF-α and body composition index were determined. Results showed that all drugs and their combinations had positive impact effect on all measured parameters, and better results were achieved from binary drug combinations than administration of each drug alone. Combination of PIO with either ATOR or LOS provided better improvements on T2DM-associated metabolic abnormalities and inflammatory status with respect to each drug alone. However, the most pronounced effects of drugs and their combinations regarding the above parameters were attributed to LOS + PIO combination. In conclusion, this study indicates that combination of ATOR + PIO and, in particular, LOS + PIO can be used as promising effective therapies in the management of HFD-induced T2DM. This concept may be attributed to the combined effects of the respective monotherapies to improve lipid profile, insulin sensitivity, and TNF-α level.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, El-Minia, Egypt.
Ahmed A
AA
Mourad
Gehan H
GH
Heeba
Ashraf
A
Taye
Mohamed A
MA
El-Moselhy
D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000818:Animals; D000069059:Atorvastatin; D008078:Cholesterol, LDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D059305:Diet, High-Fat / Q000009:adverse effects; D004359:Drug Therapy, Combination; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy / Q000209:etiology / Q000276:immunology; D006943:Hyperglycemia / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D009765:Obesity / Q000150:complications / Q000209:etiology / Q000276:immunology; D000077205:Pioglitazone; D011758:Pyrroles / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D045162:Thiazolidinediones / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D047228:Angiotensin II Type 1 Receptor Blockers; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D011758:Pyrroles; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D000069059:Atorvastatin; D019808:Losartan; D000077205:Pioglitazone