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[h=1]Role of IGF-I in follistatin-induced skeletal muscle hypertrophy.[/h]Barbé C1, Kalista S2, Loumaye A2, Ritvos O3, Lause P2, Ferracin B2, Thissen JP2.
[h=3]Author information[/h]
[h=3]Abstract[/h]<abstracttext>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 musclesensitivity 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 hypertrophyrequires 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.</abstracttext>
Copyright © 2015 the American Physiological Society.
[h=4]KEYWORDS:[/h]IGF-I; follistatin; insulin; myostatin; skeletal muscle hypertrophy
<dl class="rprtid" style="margin-right: 15px; margin-left: 0px; font-size: 0.8465em; line-height: 1.4em; display: inline;"><dt style="display: inline; padding: 0px; margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px !important; white-space: nowrap;">PMID:</dt> <dd style="margin: 0px; display: inline; padding: 0px; white-space: nowrap;">26219865</dd> <dd style="margin: 0px; display: inline; padding: 0px; white-space: nowrap;">[PubMed - indexed for MEDLINE] </dd><dd style="margin: 0px; display: inline; padding: 0px; white-space: nowrap;"></dd><dt style="display: inline; padding: 0px; margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0.5em !important; white-space: nowrap;">PMCID:</dt> <dd style="margin: 0px; display: inline; padding: 0px; white-space: nowrap;">PMC4572457</dd><dd style="margin: 0px; display: inline; padding: 0px; white-space: nowrap;"> [Available on 2016-09-15]</dd></dl>
[h=3]Author information[/h]
[h=3]Abstract[/h]<abstracttext>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 musclesensitivity 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 hypertrophyrequires 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.</abstracttext>
Copyright © 2015 the American Physiological Society.
[h=4]KEYWORDS:[/h]IGF-I; follistatin; insulin; myostatin; skeletal muscle hypertrophy
<dl class="rprtid" style="margin-right: 15px; margin-left: 0px; font-size: 0.8465em; line-height: 1.4em; display: inline;"><dt style="display: inline; padding: 0px; margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px !important; white-space: nowrap;">PMID:</dt> <dd style="margin: 0px; display: inline; padding: 0px; white-space: nowrap;">26219865</dd> <dd style="margin: 0px; display: inline; padding: 0px; white-space: nowrap;">[PubMed - indexed for MEDLINE] </dd><dd style="margin: 0px; display: inline; padding: 0px; white-space: nowrap;"></dd><dt style="display: inline; padding: 0px; margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0.5em !important; white-space: nowrap;">PMCID:</dt> <dd style="margin: 0px; display: inline; padding: 0px; white-space: nowrap;">PMC4572457</dd><dd style="margin: 0px; display: inline; padding: 0px; white-space: nowrap;"> [Available on 2016-09-15]</dd></dl>
