Effects of short-term testosterone exposure on insulin sensitivity of muscles in female rats

The effects of testosterone on insulin sensitivity were studied in oophorectomized female rats. Euglycemic, hyperinsulinemic clamp measurement showed a marked decrease of insulin sensitivity after 48 but not 24 h of testosterone exposure, which was overcome at high insulin concentrations. Insulin stimulation of 2-deoxyglucose uptake as well as glycogen synthesis was measured in the white and red parts of the gastrocnemius, the extensor digitorum longus, and soleus muscles as well as in the liver (only glycogen synthesis). After 24 h of treatment, inhibition of both 2-deoxyglucose uptake and glycogen synthesis was found in the most insulin-sensitive muscles. After 48 h of insulin stimulation, glycogen synthesis was inhibited in all examined individual muscles (white and red parts of gastrocnemius, extensor digitorum longus, and soleus) as was the activity of the insulin-sensitive part of glycogen synthase in muscle. Inhibition of insulin-stimulated 2-deoxyglucose uptake again affected the most insulin-sensitive muscles. There was a slight but significant change of muscle fiber composition toward less long-chain myosin and more short-chain myosin-containing fibers. Serum cortisol, plasma free fatty acids, and blood glycerol did not change. It is concluded that testosterone administration in moderate doses to oophorectomized female rats is followed by a rapid deterioration of insulin sensitivity in muscle, mediated mainly by perturbations of the insulin receptor-glycogen synthesis systems apparently coinciding with changes in muscle morphology.