Highlights
• Deletion of skeletal muscle Akt2 alone does not reduce downstream insulin signaling or alter glucose homeostasis.
• Inhibition of both skeletal muscle Akt isoforms prevents downstream signaling and results in muscle atrophy.
• Chronic ablation of Akt in skeletal muscle does not block insulin-stimulated glucose uptake in vivo.
• Prolonged Akt deficiency activates AMPK, which is required for insulin-stimulated glucose uptake in muscle lacking Akt.
Abstract
Objective
Skeletal muscle insulin signaling is a major determinant of muscle growth and glucose homeostasis. Protein kinase B/Akt plays a prominent role in mediating many of the metabolic effects of insulin. Mice and humans harboring systemic loss-of-function mutations in Akt2, the most abundant Akt isoform in metabolic tissues, are glucose intolerant and insulin resistant. Since the skeletal muscle accounts for a significant amount of postprandial glucose disposal, a popular hypothesis in the diabetes field suggests that a reduction in Akt, specifically in skeletal muscle, leads to systemic glucose intolerance and insulin resistance. Despite this common belief, the specific role of skeletal muscle Akt in muscle growth and insulin sensitivity remains undefined.
