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Publication : Deletion of muscle IGF-I transiently impairs growth and progressively disrupts glucose homeostasis in male mice.

First Author  Vassilakos G Year  2019
Journal  FASEB J Volume  33
Issue  1 Pages  181-194
PubMed ID  29932867 Mgi Jnum  J:286693
Mgi Id  MGI:6388249 Doi  10.1096/fj.201800459R
Citation  Vassilakos G, et al. (2019) Deletion of muscle IGF-I transiently impairs growth and progressively disrupts glucose homeostasis in male mice. FASEB J 33(1):181-194
abstractText  Insulin-like growth factors (IGFs) are essential for local skeletal muscle growth and organismal physiology, but these actions are entwined with glucose homeostasis through convergence with insulin signaling. The objective of this work was to determine whether the effects of IGF-I on growth and metabolism could be separated. We generated muscle-specific IGF-I-deficient (MID) mice that afford inducible deletion of Igf1 at any age. After Igf1 deletion at birth or in young adult mice, evaluations of muscle physiology and glucose homeostasis were performed up to 16 wk of age. MID mice generated at birth had lower muscle and circulating IGF-I, decreased muscle and body mass, and impaired muscle force production. Eight-wk-old male MID had heightened insulin levels with trends of elevated fasting glucose. This phenotype progressed to impaired glucose handling and increased fat deposition without significant muscle mass loss at 16 wk of age. The same phenotype emerged in 16-wk-old MID mice induced at 12 wk of age, compounded with heightened muscle fatigability and exercise intolerance. We assert that muscle IGF-I independently modulates anabolism and metabolism in an age-dependent manner, thus positioning muscle IGF-I maintenance to be critical for both muscle growth and metabolic homeostasis.-Vassilakos, G., Lei, H., Yang, Y., Puglise, J., Matheny, M., Durzynska, J., Ozery, M., Bennett, K., Spradlin, R., Bonanno, H., Park, S., Ahima, R. S., Barton, E. R. Deletion of muscle IGF-I transiently impairs growth and progressively disrupts glucose homeostasis in male mice.
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