Effect of pioglitazone on oxidative stress of skeletal muscle in the insulin resistance rat model induced by high sucrose diet
Abstract
Background: Metabolic syndrome is associated with some medical disorders such as central obesity, being overweight, insulin resistance and hypertension. This study was designed to determine the effect of pioglitazone on oxidative stress in the insulin resistance rat model.
Methods: In this study, the model was induced by high sucrose (935 mm) diet for 20 weeks. Three groups were used in the experiment. Control group received standard laboratory diet and drinking water. Metabolic syndrome induced group received 32% sucrose containing drinking water for 20 weeks. Pioglitazone-treated metabolic syndrome group has received pioglitazone treatment (30 mg/kg/day, via oral gavage) for two weeks at the end of the 18th week of metabolic syndrome group. After experimental period, skeletal muscle tissues were homogenized to measure important enzymes such as aspartate aminotransferase, lactate dehydrogenase and as the marker of oxidative stress; total-antioxidant-status, total-oxidant-status and malondialdehyde. Western blot technique was used to determine protein level of thioredoxin1.
Results: Aspartate aminotransferase and lactate dehydrogenase levels increased in metabolic syndrome group but pioglitazone treatment decreased these levels. In metabolic syndrome group the oxidative stress status increased but the treatment of pioglitazone decreased the level of oxidative stress in the skeletal muscle. In addition, thioredoxin1 decreased in metabolic syndrome group but administration of pioglitazone increased this level.
Conclusions: There was an elevated effect of oxidative stress in high sucrose fed rats but the treatment of pioglitazone improved glucose tolerance and insulin sensitivity.
Keywords
Supporting Institution
Project Number
Thanks
References
- 1. Savage DB, Petersen KF, Shulman GI. Mechanisms of insulin resistance in humans and possible links with inflammation. Hypertension. 2005;45(5):828–33.
- 2. Alberti KGMM, Zimmet P, Shaw J. Metabolic syndrome: A new world-wide definition. A consensus statement from the International Diabetes Federation. Diabet Med. 2006;23:469–80.
- 3. Scott CL. Diagnosis, prevention and intervention for the metabolic syndrome. Am J Cardiol. 2003;92:35–42.
- 4. Avramoglu RK, Basciano H, Adeli K. Lipid and lipoprotein dysregulation in insulin resistant states. Clinica Chimica Acta. 2006;368:1–19.
- 5. Yeo YH, Lai YC. Redox regulation of metabolic syndrome: recent developments in skeletal muscle insulin resistance and non-alcoholic fatty liver disease (NAFLD). Curr Opin Physiol. 2019;9:79-86.
- 6. Ohta Y, Kinugawa S, Matsushima S, Ono T, Sobirin MA, Inoue N, et al. Oxidative stress impairs insulin signal in skeletal muscle and causes insulin resistance in post infarct heart failure. Am J Physiol Heart Circ Physiol. 2011;300:H1637-44.
- 7. Ferreira LF, Laitano O. Regulation of NADPH oxidases in skeletal muscle. Free Radic Biol Med. 2016;98:18-28.
- 8. Saltiel AR, Olefsky JM. Thiazolidinediones in the treatment of insulin resistance and type 2 diabetes. Diabetes. 1996;45:1661–9.
- 9. Plosker GL, Faulds D. Troglitazone: a review of its use in the management of type 2 diabetes mellitus. Drugs. 1999;57:409–38.
- 10. Spiegelman BM. PPAR-gamma: adipogenic regulator and thiazolidinediones receptor. Diabetes. 1998;47:507–14.