Insulin-like growth factor I prevents corticosteroid-induced diaphragm muscle atrophy in emphysematous hamsters.
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.
Fournier
Mario
M
Cedars-Sinai Medical Center, 8700 Beverly Blvd., Rm. 6732, Los Angeles, CA 90048, USA. mario.fournier@cshs.org
Huang
Zhi-Shen
ZS
Li
Hongyan
H
Da
Xiaoyu
X
Cercek
Bojan
B
Lewis
Michael I
MI
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
D000305:Adrenal Cortex Hormones; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I