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Abstract

Pancreatic islets consist of 60-80% beta cells, which secrete insulin, a hormone of profound importance in the regulation of carbohydrate, fat and protein metabolism. Beta cell death and/or dysfunction result in an insufficient amount of insulin that leads to high glucose levels in the blood, a metabolic disorder known as Diabetes mellitus. Many studies aiming to establish new therapeutic applications for this disorder are targeted at understanding and manipulating the mechanisms of beta cell proliferation and function. The present comprehensive review summarizes the advances in the field of beta cell renewal and focuses on three fundamental issues: (i) identification of the cellular origins of new beta cells in the adult, (ii) regulation of beta cell proliferation, and (iii) downstream signaling events controlling the cell cycle machinery. Although the source of new adult beta cells is still being debated, recent findings in mice show an important contribution of beta cell proliferation to adult beta cell mass. In conjunction with describing characterized beta cell mitogens and components of the beta cell cycle machinery, we discuss how manipulating the proliferative potential of beta cells could provide novel methods for expanding beta cell mass. Such an expansion could be achieved either through in vitro systems, where functional beta cells could be generated, propagated and further used for transplantation, or in vivo, through directed beta cell renewal from sources in the organism. Once established, these methods would have profound benefits for diabetic patients.