Antioxidant Tempol Lowers Age-Related Increases in Insulin Resistance in Fischer 344 Rats

Abstract

It is well documented that both oxidative stress and insulin resistance increase with advancing age. In the present study, a hypothesis was tested that an increase in oxidative stress leads to an age-associated increase in insulin resistance. Adult (6-month) and old (24-month) Fischer 344 rats were supplemented with vehicle and antioxidant (tempol, 1 mmol/L in drinking water, four weeks). Markers of oxidative stress and insulin resistance were measured. The level of malondialdehyde (MDA) showed an increase in the plasma and renal proximal tubules (RPT) of vehicle-supplemented old rats but not adult rats. Also, the carboxymethyllysine (CML) level increased in the RPT of vehicle-supplemented old rats. Tempol-supplementation to old rats decreased the levels of MDA and CML compared to vehicle-supplemented old rats. Further, plasma glucose, insulin, and triglycerides were higher in the vehicle-supplemented old rats than the adult rats. Tempol-supplementation to old rats decreased plasma glucose, insulin, and triglycerides, unlike vehicle-supplemented old rats. Homeostasis model assessment, an index of insulin resistance, was increased in vehicle-supplemented old rats but decreased following tempol-supplementation. This study suggests that there are age-related increases in oxidative stress and insulin resistance in Fischer 344 rats. It is speculated that increased oxidative stress may be responsible for the development of insulin resistance in old Fischer 344 rats

Keywords:

• oxidative stress
• insulin resistance
• G-protein coupled receptor kinase 2
• protein kinase C