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Am J Physiol Endocrinol Metab 279: E912-E919, 2000;
0193-1849/00 $5.00
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Vol. 279, Issue 4, E912-E919, October 2000

Reduced insulin-stimulated glucose transport in denervated muscle is associated with impaired Akt-alpha activation

Jason J. Wilkes and Arend Bonen

Department of Kinesiology, University of Waterloo, Waterloo, Ontario, N2L 3G1 Canada

Insulin signaling was examined in muscle made insulin resistant by short-term (24-h) denervation. Insulin-stimulated glucose transport in vitro was reduced by 28% (P < 0.05) in denervated muscle (DEN). In control muscle (SHAM), insulin increased levels of surface-detectable GLUT-4 (i.e., translocated GLUT-4) 1.8-fold (P < 0.05), whereas DEN surface GLUT-4 was not increased by insulin (P > 0.05). Insulin treatment in vivo induced a rapid appearance of phospho[Ser473]Akt-alpha in SHAM 3 min after insulin injection. In DEN, phospho[Ser473]Akt-alpha also appeared at 3 min, but Ser473-phosphorylated Akt-alpha was 36% lower than in SHAM (P < 0.05). In addition, total Akt-alpha protein in DEN was 37% lower than in SHAM (P < 0.05). Akt-alpha kinase activity was lower in DEN at two insulin levels tested: 0.1 U insulin/rat (-22%, P < 0.05) and 1 U insulin/rat (-26%, P < 0.01). These data indicate that short-term (24-h) denervation, which lowers insulin-stimulated glucose transport, is associated with decreased Akt-alpha activation and impaired insulin-stimulated GLUT-4 appearance at the muscle surface.

GLUT-4; soleus; tibialis anterior


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