title: Impaired insulin-stimulated glucose transport in ATM-deficient mouse skeletal muscle.
abstract: There are reports that ataxia telangiectasia mutated (ATM) plays a role in insulin-stimulated Akt phosphorylation, although this is not the case in some cell types. Because Akt plays a key role in insulin signaling, which leads to glucose transport in skeletal muscle, the predominant tissue in insulin-stimulated glucose disposal, we examined whether insulin-stimulated Akt phosphorylation and (or) glucose transport would be decreased in skeletal muscle of mice lacking functional ATM, compared with muscle from wild-type mice. We found that in vitro insulin-stimulated Akt phosphorylation was normal in soleus muscle from mice with 1 nonfunctional allele of ATM (ATM+/-) and from mice with 2 nonfunctional alleles (ATM-/-). However, insulin did not stimulate glucose transport or the phosphorylation of AS160 in ATM-/- soleus. ATM protein level was markedly higher in wild-type extensor digitorum longus (EDL) than in wild-type soleus. In EDL from ATM-/- mice, insulin did not stimulate glucose transport. However, in contrast to findings for soleus, insulin-stimulated Akt phosphorylation was blunted in ATM-/- EDL, concomitant with a tendency for insulin-stimulated phosphatidylinositol 3-kinase activity to be decreased. Together, the findings suggest that ATM plays a role in insulin-stimulated glucose transport at the level of AS160 in muscle comprised of slow and fast oxidative-glycolytic fibers (soleus) and at the level of Akt in muscle containing fast glycolytic fibers (EDL).
authors.affiliation: Department of Biology, Saint Louis University, 3507 Laclede Ave., St. Louis, MO 63103, USA.
authors.forename: James Kain
authors.initials: JK
authors.lastname: Ching
authors.forename: Larry D
authors.initials: LD
authors.lastname: Spears
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Armon
authors.forename: Allyson L
authors.initials: AL
authors.lastname: Renth
authors.forename: Stanley
authors.initials: S
authors.lastname: Andrisse
authors.forename: Roy L
authors.initials: RL
authors.lastname: Collins
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Fisher
mesh_terms: D000818:Animals; D001692:Biological Transport; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism; D010766:Phosphorylation
chemical_list: D007328:Insulin; D005947:Glucose