Effects of insulin-like growth factor-I and growth hormone in models of parenteral nutrition

Administration of growth factors such as growth hormone (GH) and insulin-like growth factor-I (IGF-I) is being investigated as a strategy to promote nitrogen accretion in catabolic patients who may require total parenteral nutrition (TPN). IGF-I has advantages compared with GH because IGF-I enhances insulin sensitivity, is effective in conditions of GH resistance, and selectively stimulates the gastrointestinal and immune systems.

Experiments were conducted to evaluate the anabolic and metabolic effects associated with administration of recombinant human GH or IGF-I in rats subjected to clinically relevant stress and maintained with TPN.

Administration of IGF-I, but not GH, attenuates dexamethasone-induced protein catabolism and increases insulin sensitivity. Simultaneous treatment with GH and IGF-I additively increases the serum concentration of IGF-I, whole-body anabolism, and lipid oxidation. GH or IGF-I when given alone produces similar increases in the serum concentration of IGF-I. However, GH selectively increases skeletal muscle mass whereas IGF-I selectively attenuates the intestinal atrophy and abnormal intestinal ion transport induced by TPN. These tissue-selective anabolic effects of GH and IGF-I are associated with differential increases in protein synthesis in skeletal muscle and jejunum, respectively.

Simultaneous treatment with GH and IGF-I may offer the greatest clinical efficacy because of improved nitrogen retention in association with enhanced lipid oxidation and stimulation of protein synthesis in multiple tissue types.