[Show abstract][Hide abstract] ABSTRACT: The objective of this study was to investigate the modulation of metabolic dysfunctions, adiponectin levels, and cardiac dysfunctions of type 2 diabetes mellitus (T2DM) by a combination of the insulin sensitizer rosiglitazone and angiotensin receptor blocker telmisartan in an experimental rat model. Fifty male adult Sprague-Dawley rats were divided equally into 5 groups. Group I: fed normal chow; served as normal control group. Groups II-V: fed a high-fat diet (HFD) for 2 weeks, followed by injection of streptozotocin (STZ; 35 mg/kg) to create a model of T2DM. Group II: treated with vehicle. Group III: treated with rosiglitazone (4 mg/kg). Group IV: treated with telmisartan (5 mg/kg). Group V: treated with both agents. Untreated HFD-STZ rats showed elevated fasting blood glucose, insulin, homeostasis model assessment (HOMA) index, triglycerides (TGs), low-density lipoprotein cholesterol (LDL), and total serum cholesterol (TC), with a decrease in high-density lipoprotein cholesterol (HDL) and adiponectin levels (p < 0.001). Rosiglitazone exerted more improvement in all parameters than telmisartan did, and a combination of both did not augment the improvement further, except for TGs and adiponectin. For the isolated atrial study, a combination of rosiglitazone and telmisartan corrected the responses of the atria of HFD-STZ rats to the negative inotropic effect induced by adenosine better than either one did alone, whereas this combination, surprisingly, significantly attenuated the positive inotropic response to β-adrenoreceptor and α-adrenoreceptor agonists. In conclusion, rosiglitazone significantly improved the metabolic and cardiac dysfunctions in T2DM. Moreover, a combination of rosiglitazone and telmisartan offered more improvement in serum TGs and adiponectin, and restored the atrial inotropic response to adenosine. Surprisingly, this combination significantly attenuates the positive inotropic response to α1-adrenoreceptor and β-adrenoreceptor agonists.
Canadian Journal of Physiology and Pharmacology 03/2011; 89(3):216-26. · 1.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the combined effect of both pioglitazone and methotrexate on disease activity of rheumatoid arthritis in a biphasic study; experimental and clinical.
EXPERIMENTALLY: 50 rats were divided into 5 equal groups; controls, experimental arthritis, methorexate treated (0.1 mg/Kg daily), pioglitazone-treated (10 mg/kg daily), and methotrexate and pioglitazone treated. Clinically: forty-nine diabetic rheumatoid arthritis patients were included. Patients group consisted of 28 patients and they received pioglitazone 30 mg orally beside their usual treatment. Control group consisted of 21 patients and they continued their usual treatment plus placebo. Disease activity was assessed using DAS28 score. Patients were followed up for 3 months.
Pioglitazone produced a significant improvement of serum oxidative stress parameters (P < 0.05), and inflammatory cytokines in the treated arthritic group (P < 0.05). Clinically, the pioglitazone treated group showed significant improvement in DAS28 (P = 0.001) and C-reactive protein (P < 0.0001) compared to placebo group.
The concomitant use of the PPAR γ agonist pioglitazone and methotrexate appears to be promising therapeutic strategy for rheumatoid arthritis patients.
Clinical medicine insights. Arthritis and musculoskeletal disorders. 01/2011; 4:1-10.