Studies of insulin insensitivity in soleus muscles of obese mice.

The isolated mouse soleus muscle is a suitable system to measure specific insulin binding and insulin effects. Studies in obese mice have pointed to discrete sites of insulin resistance of skeletal muscle in obesity: (1) A decrease in the number of insulin receptors, which may result in diminished insulin sensitivity (i.e., impaired responses to submaximally stimulating doses of insulin); and (2) Alterations that lay apart from, or beyond, the insulin receptor: thus, glucose transport (and/or phosphorylation) appears to be intrinsically altered and the stimulation by insulin of glycogen synthesis is markedly depressed. These alterations are responsible for the marked resistance to maximally stimulating doses of insulin. The serum from a patient with the syndrome of insulin resistance and acanthosis nigricans contains antibodies that inhibit insulin binding and exert insulin-like effects in muscle; this serum is, however, less effective than insulin in maximally stimulating glycogen synthesis, which suggests some differences in their mechanisms of action.