Effects of testosterone on muscle insulin sensitivity and morphology in female rats

Intact or oophorectomized (OVX) female rats were given moderate doses of testosterone for 12 wk. Insulin-stimulated glucose transport with submaximal insulin concentrations was studied with the euglycemic clamp technique. Glycogen synthesis and 2-deoxy-D-glucose uptake were measured during the clamp in the extensor digitorum longus, white and red portions of the gastrocnemius, and in the soleus muscles by tracer technique. Testosterone treatment resulted in elevations of circulating testosterone, increased plasma insulin concentrations, and a marked decrease in insulin-stimulated glucose transport. In control animals, glycogen synthesis and 2-deoxy-D-glucose transport increased with increasing concentrations of type 1 fibers. Testosterone inhibited glycogen synthesis and 2-deoxy-D-glucose transport to approximately 50% in all muscles except 2-deoxy-D-glucose transport in intact rats. Glycogen synthesis in the liver was not affected. Testosterone administration also resulted in changes in muscle morphology. The relative number of type 1 fibers decreased, whereas type 2 fibers increased. This was most pronounced in red muscles. There was also a decrease in capillary density after testosterone treatment. It was concluded that testosterone administered to female rats is followed by marked insulin resistance. This is correlated to alterations in muscle morphology with fewer type 1 fibers and a lower degree of capillarization, which are both known to be characteristics of insulin-insensitive muscles.