title: Role of IGF-I in follistatin-induced skeletal muscle hypertrophy.
abstract: Follistatin, a physiological inhibitor of myostatin, induces a dramatic increase in skeletal muscle mass, requiring the type 1 IGF-I receptor/Akt/mTOR pathway. The aim of the present study was to investigate the role of IGF-I and insulin, two ligands of the IGF-I receptor, in the follistatin hypertrophic action on skeletal muscle. In a first step, we showed that follistatin increases muscle mass while being associated with a downregulation of muscle IGF-I expression. In addition, follistatin retained its full hypertrophic effect toward muscle in hypophysectomized animals despite very low concentrations of circulating and muscle IGF-I. Furthermore, follistatin did not increase muscle sensitivity to IGF-I in stimulating phosphorylation of Akt but, surprisingly, decreased it once hypertrophy was present. Taken together, these observations indicate that increased muscle IGF-I production or sensitivity does not contribute to the muscle hypertrophy caused by follistatin. Unlike low IGF-I, low insulin, as obtained by streptozotocin injection, attenuated the hypertrophic action of follistatin on skeletal muscle. Moreover, the full anabolic response to follistatin was restored in this condition by insulin but also by IGF-I infusion. Therefore, follistatin-induced muscle hypertrophy requires the activation of the insulin/IGF-I pathway by either insulin or IGF-I. When insulin or IGF-I alone is missing, follistatin retains its full anabolic effect, but when both are deficient, as in streptozotocin-treated animals, follistatin fails to stimulate muscle growth.
authors.affiliation: Pole of Endocrinology, Diabetes and Nutrition; Institut de Recherche Expérimentale et Clinique IREC, Université Catholique de Louvain, Brussels, Belgium; and caroline.barbe@uclouvain.be.
authors.forename: Caroline
authors.initials: C
authors.lastname: Barbé
authors.affiliation: Pole of Endocrinology, Diabetes and Nutrition; Institut de Recherche Expérimentale et Clinique IREC, Université Catholique de Louvain, Brussels, Belgium; and.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Kalista
authors.affiliation: Pole of Endocrinology, Diabetes and Nutrition; Institut de Recherche Expérimentale et Clinique IREC, Université Catholique de Louvain, Brussels, Belgium; and.
authors.forename: Audrey
authors.initials: A
authors.lastname: Loumaye
authors.affiliation: Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Ritvos
authors.affiliation: Pole of Endocrinology, Diabetes and Nutrition; Institut de Recherche Expérimentale et Clinique IREC, Université Catholique de Louvain, Brussels, Belgium; and.
authors.forename: Pascale
authors.initials: P
authors.lastname: Lause
authors.affiliation: Pole of Endocrinology, Diabetes and Nutrition; Institut de Recherche Expérimentale et Clinique IREC, Université Catholique de Louvain, Brussels, Belgium; and.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Ferracin
authors.affiliation: Pole of Endocrinology, Diabetes and Nutrition; Institut de Recherche Expérimentale et Clinique IREC, Université Catholique de Louvain, Brussels, Belgium; and.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Thissen
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D015536:Down-Regulation; D038681:Follistatin / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D006984:Hypertrophy / Q000378:metabolism; D007016:Hypophysectomy; D007328:Insulin / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D055435:Myostatin / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D038681:Follistatin; D007328:Insulin; C525912:Mstn protein, mouse; D055435:Myostatin; C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt
keywords: IGF-I; follistatin; insulin; myostatin; skeletal muscle hypertrophy