EFFECT OF THIAZOLIDINEDIONES ON ADIPOCYTOKINES AND LIPID PROFILE IN INSULIN RESISTANT SPRAGUE DAWLEY RATS
Background: Insulin resistance is manifested by decreased effect of fixed quantity of insulin on glucose metabolism leading to type 2 diabetes mellitus. Visceral obesity has been positively correlated with insulin resistance but its mechanism is not fully defined. Insulin resistance may be the consequence of adipocytokines including visfatin and resistin. This study was designed to observe the effects of thiazolidinediones on lipid profile and levels of adipocytokines (visfatin and resistin) in insulin resistant Sprague Dawley rats. Methods: Ninety Sprague Dawley rats were randomly divided into three groups. Group I served as control. Rats in Group II and III were made insulin resistant diabetics. Group III was treated with rosiglitazone after development of diabetes. Plasma glucose, serum triglycerides (TG), HDL, TG: HDL ratio and serum adipocytokines (visfatin, resistin) levels were analyzed. Results: Body weight and plasma glucose were significantly increased (p<0.05) along with TG: HDL ratio (p<0.05) in group II and group III at the end of 4th week. Serum visfatin and resistin levels also increased significantly (p<0.05) in group II and III at the end of 4th week. Treatment of group III with rosiglitazone led to improvement in insulin resistance with decrease in serum resistin levels (p<0.05) and increase in serum visfatin levels (p<0.05). Rosiglitazone treatment decreased serum TG level and increased serum HDL level. Conclusions: Deranged lipid profile and increased serum resistin levels indicate insulin resistance and impending hyperglycaemia. Thiazolidinediones augment sensitivity of insulin to restore normoglycemia by improving lipid profile, decreasing serum resistin levels and improving serum visfatin levels.
Pak J Physiol 2017;13(4):3–6
2. Hameed W, Yousaf I, Latif R, Aslam M. Effect of visfatin on testicular steroidogenesis in diabetic rats and isolated Leydig cell culture. J Ayub Med Coll Abbottabad 2012;24:3–4.
3. Chen MP, Chung FM, Chang DM. Elevated plasma level of visfatin/pre-B cell colony-enhancing factor in patients with type 2 diabetes mellitus. J Clin Endocrinol Metabol 2006;91:295–9.
4. Samaras K, Campbell LV. Increasing incidence of type 2 diabetes in the third millennium: is abdominal fat the central issue? Diabetes Care 2000;23:441–2.
5. Olefsky JM. Treatment of insulin resistance with peroxisome proliferator-activated receptor gamma agonists. J Clin Invest 2000;106:467–72.
6. Steppan CM, Bailey ST, Bhat S. The hormone resistin links obesity to diabetes. Nature 2001;409:307–12.
7. Juan CC, Au LC, Fang VS. Suppressed gene expression of adipocyte resistin in an insulin-resistant rat model probably by elevated free fatty acids. Biochem Biophys Res Commun 2001;289:1328–33.
8. Hirosumi J, Tuncman G, Chang L. A central role for JNK in obesity and insulin resistance. Nature 2002;420:333–6.
9. Shojima N, Sakoda H, Ogihara T. Humoral regulation of resistin expression in 3T3-L1 and mouse adipose cells. Diabetes 2002;51:1737–44.
10. Haugen F, Jorgensen A, Drevon CA, Trayhurn P. Inhibition by insulin of resistin gene expression in 3T3-L1 adipocytes. FEBS Lett 2001;507:105–8.
11. Hartman HB, Hu X, Tyler KX, Dalal CK, Lazar MA. Mechanisms regulating adipocyte expression of resistin. J Biol Chem 2002;277:19754–61.
12. McLaugin T, Abbasi F, Cheal K, Chu J, Lamendola C, Reaven G. Use of metabolic markers to identify overweight individuals who are insulin resistant. Ann Intern Med 2003;139:802–9.
13. Gutman RA, Basilico MZ, Bernal A, Chicco A, Lombardo YB. Long-term hypertriglyceridemia and glucose intolerance in rats fed chronically an isocaloric sucrose-rich diet. Metab Clin Exp 1987;36:1013–20.
14. Hwang IS, Hoffman BB, Reaven GM. Fructose-induced insulin resistance and hypertension in rats. Hypertension 1987;10:512–6.
15. Hulman S, Falkner B. The effect of excess dietary sucrose on growth, blood pressure, and metabolism in developing Sprague Dawley rats. Pediatric Res 1994;36:95–101.
16. Dominik G, Haider I, Friedrich MI, Georg SI, Michaela A, Sabina M. Free fatty acids normalize a rosiglitazone-induced visfatin release. Am J Physiol Endocrinol Metabol 2006; 291:E885–E890.
17. Choi KC, Ryu OH, Lee KW. Effect of PPAR-α and -γ agonist on the expression of visfatin, adiponectin, and TNF-α in visceral fat of OLETF rats. Biochem Biophys Res Commun 2005;336:747–53.
18. Santure M, Pitre M, Marette A, Deshaies Y, Lemieux C, Lariviere R. Induction of insulin resistance by high sucrose feeding does not raise mean arterial blood pressure but impairs haemodynamic responses to insulin in rats. Br J Pharmacol 2002;137:185–96.
19. Curat CA, Wegner V, Sengenes C, Miranville A, Tonus C, Busse R. Macrophages in human visceral adipose tissue: increased accumulation in obesity and a source of resistin and visfatin. Diabetologia 2006;49:744–7.
20. Rangwala SM, Rich AS, Rhoades B, Shapiro JS, Obici S, Rossetti L, et al. Abnormal glucose homeostasis due to chronic hyperresistinemia. Diabetes 2004;53(8):1934–41.
21. Tontonoz P, Nagy L, Alvarez JG, Thomazy VA, Evans RM. PPARγ promotes monocyte/macrophage differentiation and uptake of oxidized LDL. Cell 1998;93:241–52.