IGF-I AND OR GROWTH-HORMONE PRESERVE DIAPHRAGM FIBER SIZE WITH MODERATE MALNUTRITION/

Resistance to the anabolic effects of growth hormone (GH) occurs with severe caloric deficit. This study examined whether moderate caloric d eficit (50% of daily intake for 7 days) in the adolescent rat exceeds a critical threshold for GH action and whether a combination of GH and insulin-like growth factor I (IGF-I) would have enhanced anabolic eff ects on the diaphragm (Dia). Five groups of rats (4 wk old) were studi ed: 1) control (Ctl), 2) nutritionally deprived (ND), 3) ND + GH, 4) N D + IGF-I, and 5) ND + GH + IGF-I. IGF-I was given by continuous infus ion (200 mu g/day). GH was injected subcutaneously (250 mu g every 12 h). Contractile and fatigue properties of the Dia were determined in v itro. Quantitative histochemical methods were used to determine Dia fi ber type proportions, cross-sectional areas, and succinate dehydrogena se activities. The body weight of Ctl rats increased 46% compared with 7% in ND animals, whereas that of ND rats receiving growth factors wa s intermediate. Serum IGF-I levels were reduced 54% in ND animals and maintained with the provision of growth factors. Dia fatigue resistanc e was improved in ND animals receiving growth factors. There were no d ifferences in Dia contractile properties, fiber type proportions, or s uccinate dehydrogenase activities across groups. ND resulted in atroph y/growth arrest of all Dia fibers (20-32%) compared with Ctl. Administ ration of IGF-I and/or GH completely prevented atrophy/growth arrest o f all Dia fibers. No additive or synergistic effects were noted. We pr opose that these growth factors may provide useful short-term adjuncti ve nutritional support in circumstances in which the provision of opti mal nutrition may be delayed or inadequate.