Forskning ved Københavns Universitet - Københavns Universitet


Role of Akt2 in contraction-stimulated cell signaling and glucose uptake in skeletal muscle

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  • Sakamoto, Kei
  • David E. Arnolds
  • Nobuharu Fujii
  • Henning F. Kramer
  • Michael F. Hirshman
  • Laurie J. Goodyear

The serine/threonine kinase Akt/PKB plays diverse roles in cells, and genetic studies have indicated distinct roles for the three Akt isoforms expressed in mammalian cells and tissues. Akt2 is a key signaling intermediate for insulin-stimulated glucose uptake and glycogen synthesis in skeletal muscle. Akt2 has also been shown to be activated by exercise and muscle contraction in both rodents and humans. In this study, we used Akt2 knockout mice to explore the role of Akt2 in exercise-stimulated glucose uptake and glycogen synthesis as well as intracellular signaling pathways that regulate glycogen metabolism in skeletal muscle. We found that Akt2 deficiency does not affect basal or exercise-stimulated glucose uptake or intracellular glycogen content in the soleus muscle. In addition, lack of Akt2 did not result in alterations in basal Akt Thr308 or basal and contraction-stimulated glycogen synthase kinase-3β (GSK-3β) Ser9 phosphorylation, glycogen synthase phosphorylation, or glycogen synthase activity. In contrast, in situ contraction failed to elicit normal increases in Akt T-loop Thr308 phosphorylation and GSK-3α Ser21 phosphorylation in tibialis anterior muscles from Akt2-deficient animals. Our data establish a key role for Akt2 in the regulation of GSK-3α Ser21 phosphorylation with contraction and add genetic evidence to support the separation of the intracellular pathways regulated by insulin and exercise that converge on glucose uptake and glycogen synthesis in skeletal muscle.

TidsskriftAmerican Journal of Physiology - Endocrinology and Metabolism
Udgave nummer5
Sider (fra-til)E1031-E1037
StatusUdgivet - 24 nov. 2006
Eksternt udgivetJa

ID: 239584471