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1 Division of Pulmonary/Critical Care Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, USA
2 Division of Cardiology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
3 Division of Pulmonary/Critical Care Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA
4 Division of Cardiology, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA, USA
* To whom correspondence should be addressed. E-mail: michael.lewis{at}cshs.org.
This study evaluated the impact of varying degrees of prolonged malnutrition on the local insulin-like growth factor-I (IGF-I) system in the costal diaphragm muscle. Adult rats were provided with either 60% or 40% of usual food intake over 3 weeks. Nutritionally deprived (ND) animals (i.e., ND60 and ND40) were compared to control (CTL) rats fed ad libitum. Costal diaphragm fiber types and cross-sectional areas (CSA) were determined histochemically. Costal diaphragm muscle IGF-I mRNA levels were determined by RT-PCR. Serum and muscle IGF-I peptide levels were determined using a rat-specific radioimmunoassay. The body weights of CTL rats increased by 5%, while those of ND60 and ND40 animals decreased by 16 and 26%, respectively. Diaphragm weights were reduced by 17 and 27% in ND60 and ND40 animals, respectively, compared to CTL. Diaphragm fiber proportions were unaffected by either ND regimen. Significant atrophy of both type IIa and IIx fibers was noted in the ND60 group, while atrophy of all 3 fiber types was observed in the diaphragm of ND40 rats. Serum IGF-I levels were reduced by 62 and 79% in ND60 and ND40 rats, respectively, compared to CTL. Diaphragm muscle IGF-I mRNA levels in both ND groups were similar to those noted in CTL. In contrast, IGF-I concentrations were reduced by 36 and 42% in the diaphragm muscle of ND60 and ND40 groups, respectively, compared to CTL. We conclude that the local (autocrine/paracrine) muscle IGF-I system is affected in our models of prolonged ND. We propose that this contributes to disordered muscle protein turnover and muscle cachexia with atrophy of muscle fibers. This is particularly so in view of recent data demonstrating the importance of the autocrine/paracrine system in muscle growth and maintenance of fiber size.
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