Regulation of pancreatic beta-cell growth and survival by the serine/threonine protein kinase Akt1/PKB alpha

The physiological performance of an organ depends on an interplay between c hanges in cellular function and organ size, determined by cell growth, prol iferation and death. Nowhere is this more evident than in the endocrine pan creas, where disturbances in function or mass result in severe disease. Rec ently, the insulin signal-transduction pathway has been implicated in both the regulation of hormone secretion from beta cells in mammals as well as t he determination of cell and organ size in Drosophila melanogaster. A promi nent mediator of the actions of insulin and insulin-like growth factor 1 (I GF-1) is the 3'-phosphoinositide-dependent protein kinase Akt, also known a s protein kinase B (PKB). Here we report that overexpression of active Akt1 in the mouse beta cell substantially affects compartment size and function . There was a significant increase in both beta -cell size and total islet mass, accompanied by improved glucose tolerance and complete resistance to experimental diabetes.