title: Insulin-like growth factor I prevents corticosteroid-induced diaphragm muscle atrophy in emphysematous hamsters.
abstract: The aim of this study was to evaluate whether recombinant human insulin-like growth factor I (rhIGF-I) could attenuate or prevent diaphragm (DIA) fiber atrophy with corticosteroid (CS) administration to emphysematous (EMP) hamsters. DIA muscle IGF-I responses to CS administration with and without exogenous rhIGF-I administration were evaluated. Three groups were studied: 1) EMP; 2) EMP + triamcinolone (T; 0.4 mg.kg-1.day-1 im); and 3) EMP + T + IGF-I (600 microg/day by constant infusion). After 4 wk, the DIA was analyzed histochemically and biochemically (IGF-I mRNA levels by RT-PCR and endogenous and exogenous IGF-I peptide levels immunochemically). Body weights of EMP-T progressively decreased, while those of EMP and EMP-T-IGF-I remained stable despite similarly reduced food intake in both T groups. DIA weight was reduced with T but preserved with rhIGF-I infusion. DIA fiber proportions were similar among the groups. The cross-sectional areas of types I, IIa, and IIx fibers were reduced (17 to 31%) with T administration but unchanged with rhIGF-I infusion. DIA IGF-I mRNA levels were similar across all groups. By contrast, the endogenous DIA IGF-I levels were reduced (41%) in the EMP-T-IGF-I animals. Total DIA IGF-I levels (endogenous + exogenous) were still significantly reduced. IGF-I immunoreactivity confirmed this reduction in all DIA fibers. We conclude that DIA fiber atrophy with T was completely prevented by exogenous rhIGF-I administration. This effect was likely mediated by the pharmacological influences of exogenously administered rhIGF-I. We speculate that this results from increased bioavailability of free IGF-I to react with muscle receptors. Reduced endogenous IGF-I levels in the DIA likely reflect a negative-feedback influence. These results may have important clinical implications for treatment options to offset the adverse effects of CS on the respiratory muscles in patients with chronic lung disorders.
authors.affiliation: Cedars-Sinai Medical Center, 8700 Beverly Blvd., Rm. 6732, Los Angeles, CA 90048, USA. mario.fournier@cshs.org
authors.forename: Mario
authors.initials: M
authors.lastname: Fournier
authors.forename: Zhi-Shen
authors.initials: ZS
authors.lastname: Huang
authors.forename: Hongyan
authors.initials: H
authors.lastname: Li
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Da
authors.forename: Bojan
authors.initials: B
authors.lastname: Cercek
authors.forename: Michael I
authors.initials: MI
authors.lastname: Lewis
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000818:Animals; D017848:Blood-Borne Pathogens; D001835:Body Weight; D006224:Cricetinae; D003964:Diaphragm / Q000378:metabolism / Q000473:pathology*; D004435:Eating; D004646:Emphysema / Q000188:drug therapy*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D008176:Lung Volume Measurements; D008297:Male; D008647:Mesocricetus; D018485:Muscle Fibers, Skeletal / Q000473:pathology; D009133:Muscular Atrophy / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D009929:Organ Size; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D000305:Adrenal Cortex Hormones; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I