Effect of insulin-like growth factor I and/or growth hormone on diaphragm of malnourished adolescent rats

Michael I. Lewis, Thomas J. Lorusso, and Mario Fournier Division of Pulmonary/Critical Care Medicine, Cedars-Sinai Medical Center, Burns and Allen Research Institute, University of California Los Angeles School of Medicine, Los Angeles, California 90048 Received 23 May 1996; accepted in final form 2 November 1996. Lewis, Michael I., Thomas J. LoRusso, and Mario Fournier. Effect of insulin-like growth factor I and/or growth hormone on diaphragm of malnourished adolescent rats. J. Appl. Physiol. 82(4): 1064-1070, 1997. Young growing animals appear to have significantly reduced "nutritional reserve" to short periods of unstressed starvation compared with adults, with resultant growth arrest and/or atrophy of diaphragm (Dia) muscle fibers. The aim of this study was to assess in an adolescent rat model of acute nutritional deprivation (ND; 72 h) the impact of insulin-like growth factor I (IGF-I), with or without added growth hormone (GH), on the cross-sectional areas (CSA) of individual Dia muscle fibers. Five groups were studied: 1 ) control (Ctr); 2 ) ND; 3 ) ND given IGF-I (ND/IGF-I); 4 ) ND given GH (ND/GH); and 5 ) ND given a combination of IGF-I and GH (ND/IGF-I/GH). IGF-I was given by a subcutaneously implanted osmotic minipump (200 µg/day), whereas GH was administered twice daily by a subcutaneous injection (250 µg every 12 h). Isometric contractile and fatigue properties of the Dia were determined in vitro. Forces were normalized for muscle CSA (i.e., specific force). Dia fiber type proportions were determined histochemically, and fiber CSA was quantified by using a computer-based image-processing system. Total serum IGF-I concentrations were significantly reduced in ND and ND/GH animals, compared with Ctr, and elevated in the groups receiving IGF-I. The provision of growth factors did not alter the contractile or fatigue properties of ND animals. Dia fiber type proportions were similar among the groups. In ND animals, there was a significant reduction in the CSA of types I, IIa, IIx, and IIc Dia fibers compared with Ctr. The administration of IGF-I alone or in combination with GH to ND animals significantly diminished the reduction in Dia fiber size. GH alone had no effect on Dia fiber size in ND animals. We conclude that with acute ND the peripheral resistance to the action of GH appears to be bypassed by the administration of IGF-I alone or in combination with GH. nutritional deprivation; diaphragm fiber cross-sectional area; diaphragm contractility