Insulin resistance: the consequence of a neuroendocrine disturbance?

Visceral obesity in man is followed by several abnormalities in endocrine secretions, including an elevated cortisol secretion as well as hyperandrogenicity in women, and a relative hypogonadism in men, suggesting a central neuroendocrine background. A pronounced insulin resistance is a main symptom of this condition and may be at least partially following these endocrine abnormalities. For example, mimicking hyperandrogenicity in women by administration of testosterone (T) in moderate doses to female rats is followed by severe muscular insulin resistance, as well as a low type I/type II muscle fiber ratio, and a low capillary density in muscle. These findings are identical to those in visceral obese women with hyperandrogenicity and insulin resistance. Studies of details of function and morphology in the muscles in this rat model have revealed that insulin stimulation of glucose transport, glycogen synthesis and the insulin sensitive part of the glycogen synthase is diminished at submaximal insulin concentrations. However, insulin receptor number and function, as well as the total number of glucose transporter 4 appear to be normal, supported by observations that the insulin resistance is overcome by elevated insulin concentrations. These observations suggest that normal cellular mechanisms for glucose metabolism in muscle in this model are under-utilized, and that the explanation to apparent insulin resistance may be found proximal to the machinery of the muscle cell. The histochemical changes of the muscles may provide a clue to the understanding of the mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)