DIABETES-MELLITUS AND IMPAIRED PANCREATIC BETA-CELL PROLIFERATION

The factors that normally regulate the proliferation of the insulin-pr oducing pancreatic beta-cell largely remain elusive although several f actors have been identified that influence beta-cell growth in vitro. The adult beta-cell is normally virtually quiescent, but its replicato ry activity can be enhanced in vitro by certain nutrients and growth f actors, and long-term alterations in beta-cell mass constitute an impo rtant means to accommodate an increased demand for insulin. Likewise, expansion of the beta-cell mass by recruitment of beta-cells to prolif erate may constitute a means by which the organism can compensate for the loss or dysfunction of beta-cells occurring in diabetes. However, neither in human or animal models for type-1 diabetes, nor in type-2 d iabetes, is beta-cell regeneration a noteworthy feature. Thus, if beta -cells could be induced to replicate at a higher rate, this may prove beneficial in maintaining normoglycaemia, since the beta-cell mass is a major determinant of the total amount of insulin that can be secrete d by the pancreas. The present review will focus on the normal regulat ion of beta-cell mitogenesis and hormones production in vitro and in v ivo, and furthermore, will present evidence for an insufficient extent of beta-cell regeneration in different forms of diabetes mellitus. Ad ditionally, the possibility of manipulating beta-cell proliferation by peptides and genetic engineering, and the significance of beta-cell m itogenesis in islet transplantation will be discussed in relation to t reatments of diabetes mellitus.