Endocrine Abstracts

Toll-like receptor 4 (TLR-4) plays an important role in innate immunity. Changes in the reduction–oxidation balance of tissues can lead to a pro-inflammatory state and insulin resistance typically seen in diabetes. An action thought to be mediated by TLRs. Omega-3 fatty acids and peroxisome proliferator activated receptor gamma (PPAR-γ) agonists as pioglitazone are currently used for decreasing inflammation in diabetes.

Aim: The aim of this study is to investigate the potential anti-diabetic effects of combining omega -3 fatty acid with the insulin sensitizer “pioglitazone” in a rat model of type 2 diabetes, and the modulating effects on TLR-4.

Method: Type 2 diabetes was induced in male Sprague-Dawley rats by combination of high fat diet and low dose streptozotocin (35 mg/kg). Diabetic rats were treated with omega-3 fatty acids (10%W/W diet), pioglitazone (20 mg/kg), and their combination for a period of 4 weeks.

Results: Omega-3 fatty acids and combination therapy significantly decreased TLR-4 activation, compared to diabetic group (P=0.05). Omega-3 fatty acids, pioglitazone, and combination therapy showed significant decrease in TLR-4 mRNA expression. Omega-3 fatty acids, pioglitazone and their combination significantly lowered hepatic malondialdehyde, total cholesterol and triglycerides levels, compared to diabetic group. Pioglitazone and combination significantly decreased blood glucose levels and improved insulin resistance.

Conclusion: In conclusion, combining PPAR-α agonists, as omega-3 fatty acids with PPAR-γ agonists as pioglitazone showed potential effects in lowering blood glucose levels and improving lipid profile and insulin resistance. Such effects are mediated through modulation of TLR-4.