Jj. Wilkes et A. Bonen, Reduced insulin-stimulated glucose transport in denervated muscle is associated with impaired Akt-alpha activation, AM J P-ENDO, 279(4), 2000, pp. E912-E919
Citations number
51
Categorie Soggetti
Endocrinology, Nutrition & Metabolism
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
Insulin signaling was examined in muscle made insulin resistant by short-te
rm (24-h) denervation. Insulin-stimulated glucose transport in vitro was re
duced by 28% (P < 0.05) in denervated muscle (DEN). In control muscle (SHAM
), insulin increased levels of surface-detectable GLUT-4 (i.e., translocate
d 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[ Ser(473)]Akt-alpha in SHAM 3 min after insulin injection. In D
EN, phospho[Ser(473)]Akt-alpha also appeared at 3 min, but Ser(473)-phospho
rylated 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 k
inase 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 indi
cate that short-term (24-h) denervation, which lowers insulin-stimulated gl
ucose transport, is associated with decreased Akt-alpha activation and impa
ired insulin-stimulated GLUT-4 appearance at the muscle surface.