Deletion of muscle IGF‐I transiently impairs growth and progressively disrupts glucose homeostasis in male mice

What is it about?

In this study, we have developed a strategy to separate the anabolic and metabolic actions of muscle derived insulin-like growth factor I (IGF-I). While there is a rich history of focus on the "insulin" properties of IGF-I as compared to its "growth factor" properties, finding clues to the physiological importance of these distinct actions has been plagued by the overlapping interactions among this family of ligands and receptors. Our mouse model affords inducible deletion of Igf1 from skeletal muscle, thus removing the ligand from one source, and uncovering the fact that in adult mice muscle IGF-I is required for glucose homeostasis in the absence of any significant change in muscle mass. The findings have broad reaching implications for metabolic health. First, these results show that maintenance of muscle mass and its production of IGF-I is important for muscle function, and whole animal activity. Second, the consequences of loss of this source of IGF-I can rapidly alter the metabolic profile of an organism, leading to increased adiposity and exercise intolerance. Perhaps the most striking finding is that even with early loss of IGF-I, disrupted glucose homeostasis manifests later in life. Thus, these findings position skeletal muscle and its production of IGF-I as central players in the maintenance of metabolic health.

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