Promiscuous affairs of PKB/AKT isoforms in metabolism

Abstract

The protein kinase B (PKB) family encompasses three isoforms; PKB (AKT1), PKB (AKT2) and PKB (AKT3). PKB and PKB but not PKB, are prominently expressed in classical insulin-sensitive tissues like liver, muscle and fat. Transgenic mice deficient for PKB, PKB or PKB have been analysed to study the roles of PKB isoforms in metabolic regulation. Until recently, only loss of PKB was reported to result in metabolic disorders, especially insulin resistance, in humans and mice. However, a new study has shown that PKB-deficient mice can show enhanced glucose tolerance accompanied by improved -cell function and higher insulin sensitivity in adipocytes. These findings prompted us to review the relevant literature on the regulation of glucose metabolism by PKB isoforms in liver, skeletal muscle, adipocytes and pancreas. However, a new study has shown that PKB-deficient mice show enhanced glucose tolerance accompanied by improved -cell function and higher insulin sensitivity in adipocytes. These findings prompted us to review the relevant literature on the regulation of glucose metabolism by PKB isoforms in liver, skeletal muscle, adipocytes and pancreas.

Insulin Receptor Signaling in Normal and Insulin-Resistant States

“…The Akt/PKB family of proteins consists of three different isoforms of serine/threonine protein kinases encoded by different genes (Schultze et al 2011). All isoforms possess a PH domain, allowing interaction with PIP 3 and recruitment to the plasma membrane.…”

Targeting Activated Akt with GDC-0068, a Novel Selective Akt Inhibitor That Is Efficacious in Multiple Tumor Models

“…The 3 isoforms of Akt have both overlapping and distinct functions and expression profiles (16,17). Activation of all 3 Akt family members have been detected in a variety of human malignancies, and inducible short hairpin RNA (shRNA) knockdown studies suggest that inhibition of all 3 Akt isoforms is required for maximum efficacy in PTENdeficient cancer xenograft models (18).…”

New Horizons in Cellular Regulation by Inositol Polyphosphates: Insights from the Pancreaticβ-Cell

“…In addition to its activity in the synthesis of Ins(1,3,4,5,6)P 5 , IPMK can act as a PI3 kinase and convert PtdIns(4,5)P 2 to PtdIns(3,4,5)P 3 and, thus, activate both Akt/PKB and presumably other PtdIns(3,4,5)P 3 -regulated proteins. These new observations are of considerable interest in the regulation of b-cells, because Akt/PKB plays an essential role in both their physiology and their pathophysiology (Elghazi et al, 2006;Buzzi et al, 2010;Leibiger et al, 2010;Schultze et al, 2011). However, IMPK can operate noncatalytically through protein-protein interaction.…”