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