Altered physiology and action of insulin-like growth factor 1 in skeletal muscle in chronic renal failure.

Chronic renal failure is associated with abnormalities of skeletal muscle that include reduction in size, fibrosis, protein depletion, and functional disorders. These disorders may be caused by several factors, including protein-calorie malnutrition, acidemia, and superimposed illnesses. However, animal research suggests that these abnormalities may occur with chronic renal failure per se in the absence of the above complications. Insulin-like growth factor 1 (IGF-1) is an anabolic hormone that, in skeletal muscle, stimulates intracellular amino acid and glucose transport and protein synthesis, suppresses protein degradation, and causes hypertrophy. In chronic renal failure, there is evidence for inhibition of the actions of IGF-1. Studies in humans with chronic renal failure given a subcutaneous injection of recombinant human IGF-1 (rhIGF-1) indicate that the rhIGF-1 induced acute suppression of plasma amino acids, insulin, and C peptide is impaired. In skeletal muscle of rats with chronic renal failure, we observed reduced IGF-1 and IGF-1 mRNA levels, resistance to the rhIGF-1-induced suppression of protein degradation, and stimulation of protein synthesis, increased IGF-1 receptor mRNA and IGF-1 receptor number and impaired receptor tyrosine kinase activity. These findings suggest that in skeletal muscle in chronic renal failure there are several abnormalities in the physiology of IGF-1 and the sensitivity to IGF-1. It is possible that these alterations contribute to the disorders of skeletal muscle structure and function in chronic renal failure. Notwithstanding these abnormalities, repeated subcutaneous injections of rhIGF-1 in malnourished patients undergoing continuous ambulatory peritoneal dialysis led to strongly positive nitrogen balance that was sustained for the 20 days of study.(ABSTRACT TRUNCATED AT 250 WORDS)