Age-Related Decline of Skeletal Muscle Insulin Sensitivity in Rats: Effect of Sex and Muscle Type

Aging is associated with a progressive decline of skeletal muscle function and insulin sensitivity. Sex differences in the insulin response to different physiological situations have been found, leading to the development of type 2 diabetes. The aim of this study was to investigate the changes in insulin sensitivity with age in male and female rats and to elucidate whether there are sex differences in the alteration profiles of systemic insulin sensitivity parameters, adiposity, skeletal muscle oxidative damage, and the insulin signaling pathway. The gastrocnemius and soleus muscles of male and female rats of 3, 9, and 18 months of age were used. The decrease of insulin sensitivity with age was higher in female than in male rats. However, the increase of both serum insulin levels and adiposity with age shows a different profile in both sexes and suggests an earlier onset of age-related impairment of insulin sensitivity in male than in female rats. Sex differences in insulin signaling key protein levels were found mainly in the most aged rats, suggesting that sex differences in these proteins would be manifested at more advanced ages than differences in the insulin-sensitivity serum profile. In addition, the gastrocnemius muscle showed more age-associated oxidative damage and insulin resistance impact than the soleus in both sexes. These results suggest the sex differences found in the impairment of insulin sensitivity of aged rats would not be attributable to differences between sexes in the time course of the levels of key proteins of the skeletal muscle insulin signaling pathway, at least in the first 18 months of life.