Insulin Resistance and a Diabetes Mellitus-Like Syndrome in Mice Lacking the Protein Kinase Akt2 (PKBβ)

TLDR

Insulin regulates glucose homeostasis by signaling through phosphorylation of scaffolding proteins and PI3K activation in muscle and liver. Akt2 knockout mice exhibit impaired insulin‑mediated glucose lowering due to liver and muscle defects, demonstrating Akt2’s essential role in glucose homeostasis.

Abstract

Glucose homeostasis depends on insulin responsiveness in target tissues, most importantly, muscle and liver. The critical initial steps in insulin action include phosphorylation of scaffolding proteins and activation of phosphatidylinositol 3-kinase. These early events lead to activation of the serine-threonine protein kinase Akt, also known as protein kinase B. We show that mice deficient in Akt2 are impaired in the ability of insulin to lower blood glucose because of defects in the action of the hormone on liver and skeletal muscle. These data establish Akt2 as an essential gene in the maintenance of normal glucose homeostasis.