[HTML][HTML] Distinct growth hormone receptor signaling modes regulate skeletal muscle development and insulin sensitivity in mice

MD Mavalli, DJ DiGirolamo, Y Fan… - The Journal of …, 2010 - Am Soc Clin Investig
MD Mavalli, DJ DiGirolamo, Y Fan, RC Riddle, KS Campbell, T Van Groen, SJ Frank…
The Journal of clinical investigation, 2010Am Soc Clin Investig
Skeletal muscle development, nutrient uptake, and nutrient utilization is largely coordinated
by growth hormone (GH) and its downstream effectors, in particular, IGF-1. However, it is not
clear which effects of GH on skeletal muscle are direct and which are secondary to GH-
induced IGF-1 expression. Thus, we generated mice lacking either GH receptor (GHR) or
IGF-1 receptor (IGF-1R) specifically in skeletal muscle. Both exhibited impaired skeletal
muscle development characterized by reductions in myofiber number and area as well as …
Skeletal muscle development, nutrient uptake, and nutrient utilization is largely coordinated by growth hormone (GH) and its downstream effectors, in particular, IGF-1. However, it is not clear which effects of GH on skeletal muscle are direct and which are secondary to GH-induced IGF-1 expression. Thus, we generated mice lacking either GH receptor (GHR) or IGF-1 receptor (IGF-1R) specifically in skeletal muscle. Both exhibited impaired skeletal muscle development characterized by reductions in myofiber number and area as well as accompanying deficiencies in functional performance. Defective skeletal muscle development, in both GHR and IGF-1R mutants, was attributable to diminished myoblast fusion and associated with compromised nuclear factor of activated T cells import and activity. Strikingly, mice lacking GHR developed metabolic features that were not observed in the IGF-1R mutants, including marked peripheral adiposity, insulin resistance, and glucose intolerance. Insulin resistance in GHR-deficient myotubes derived from reduced IR protein abundance and increased inhibitory phosphorylation of IRS-1 on Ser 1101. These results identify distinct signaling pathways through which GHR regulates skeletal muscle development and modulates nutrient metabolism.
The Journal of Clinical Investigation