Role of PKB/Akt in Liver Diseases

PKB/Akt is a ubiquitous and evolutionarily conserved serine/threonine kinase that is recognized as a major coordinator of various intracellular signals. It controls cell responses to extrinsic stimuli and regulates cell metabolism, proliferation, and survival. Proper tuning of PKB activity via direct or indirect mechanisms is of utmost importance for stringent regulation of PKB-dependent cellular activities. Many diseases, such as cancer or metabolic disorders, are the result of, or are associated with, aberrant activity of the PI3K/PTEN/PKB pathway. In many tumors, the PI3K/PTEN/PKB pathway is activated by upstream mutations in PI3K or PTEN or by the amplification/overexpression/mutation of PKB iso­forms themselves. Liver tumors are not the only pathological condition associated with disorders of this pathway. PKB has also been implicated in the development of hepatic insulin resistance, type 2 diabetes mellitus and, as has become evident over the past few years, in ischemia/reperfusion processes. In this chapter, the role of PKB in major physiological processes of cells is summarized and different liver disease conditions are considered by analyzing their pathophysiology from the perspective of PKB involvement.