Glucose Mediated Regulation of Beta Cell Proliferation

The Division of Endocrinology at the University of Pittsburg, USA has reviewed published literature investigating the effect of glucose on beta cell proliferation.  The review also describes the data supporting various known mechanisms of action.

The in vitro experiments conducted by Swenne and colleagues in the early eighties studied the effect of glucose on rodent beta cells. Islets of fetal, neonatal, and adult rats were isolated and cultured at different glucose concentrations and DNA synthesis rates were calculated by pulse labeling with 3H-thymidine.  Results indicated that beta cell proliferation increased 2.5-fold in all age groups when the concentration of glucose was increased from 2.7 mM to 16.7 mM, with no further increase in proliferation at 33.3 mM.  In addition, the results indicated that the rate of proliferation decreased with increased donor age.

In contrast, a study conducted by Scharfmann group has shown that 10 mM glucose increases 20-fold the area of insulin-positive cells in embryonic pancreases in culture (compared with 0 mM) without increasing beta cell proliferation.  At this concentration, glucose enhances the differentiation of early progenitors into beta cells by regulating the transition between Ngn3 and NeuroD.

In more recent years, Maedler K, et al analyzed the effects of glucose in human beta cells employing the cell cycle progression marker, Ki67, and insulin staining as means to detect beta cell proliferation.  Their observations indicated that a short-term (1–3 days) exposure of cultured human islets to 33.3 mM glucose increased the number of proliferating (Ki67-positive) beta cells, whereas prolonged (>4-day) exposure resulted in an inhibition of proliferation, relative to islets at 5.5 mM glucose.  It was also concluded that this decrease in human beta cell proliferation induced by chronic incubation with glucose was independent of the age of the islet donor.

This article also provides insights into how glucose induces beta cell proliferation and the network of signaling pathways involved in these processes.