Akt isoforms and glucose homeostasis – the leptin connection

The serine/threonine kinase Akt, also known as protein kinase B, has been the focus of substantial attention, largely because it is frequently activated in human cancers. However, relatively little is known about the roles of Akt, particularly the individual isoforms of Akt, in glucose homeostasis in vivo. This review summarizes data on the role of Akt isoforms in glucose homeostasis and diabetes. Emphasis is given to the observation that certain combinations of whole-body Akt1 and Akt2 deficiencies reduce circulating levels of leptin and that restoration of leptin levels restores normal glucose homeostasis in diabetic Akt-deficient mice. The significance of these findings, together with recent observations suggesting that leptin emulates insulin action, is also discussed.