Muscle wasting resistance

Insulin is a powerful anabolic hormone but it is unlikely that insulin deficiency causes skeletal muscle atrophy by direct action on muscle fibers (as opposed to neurogenic atrophy) except in chronic untreated cases. There is however a close parallel between the catabolic states induced by glucocorticoid excess and by insulin deficiency. Moreover, impaired insulin action is implicated in other endocrine myopathies as a contributory cause of muscle wasting. Both acromegaly and thyrotoxicosis are associated with insulin resistance due to a postreceptor defect, and secondary hyperparathyroidism due to hypophosphatemia also gives rise to insulin insensitivity. 

Insulin stimulates peripheral tissue protein synthesis by stimulating amino acid uptake and protein synthesis at the level of translation and by inhibiting protein degradation. At low insulin levels, muscle proteolysis occurs. As the levels increase, proteolysis decreases and protein synthesis is favored. Exercise decreases proteolysis and increases protein synthesis, whereas disuse results in muscle wasting and depressed protein synthesis. Exercise increases sensitivity to insulin, whereas disuse makes the tissue insulin-resistant. Obesity, pregnancy, and glucocorticoids also increase insulin resistance. 

The vascularization of muscle tissue increases. As the number of capillaries increases, the transit time for blood through muscle increases (i.e., there is increased resistance to flow because of a greater surface area for the exchange of nutrients). The exchange of nutrients and waste products between the blood and muscle fibers is more efficient. 

Cuthbertson D, Smith K, Babraj J et al. (2005) Anabolic signaling deficits underlie amino add resistance of wasting, aging muscle. EASES J. 19,422—424. 

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