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

Abstract

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-α in SHAM 3 min after insulin injection. In DEN, phospho[Ser473]Akt-α also appeared at 3 min, but Ser473-phosphorylated Akt-α was 36% lower than in SHAM ( P < 0.05). In addition, total Akt-α protein in DEN was 37% lower than in SHAM ( P < 0.05). Akt-α 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-α activation and impaired insulin-stimulated GLUT-4 appearance at the muscle surface.