Pancreatic beta cell replication: effects of hexose sugars

Abstract

Neonatal rat pancreatic monolayer cultures were utilized to investigate the effects of various hexose sugars on insulin release and beta cell replication. Sugars tested were D-glucose, L-glucose, 3-O-methyl-D-glucose, D-mannose and D-fructose. These agents were added at varying concentrations to a control medium containing a baseline level of 5.5 mM D-glucose. Replication was estimated by incubating cultures with [3H]thymidine and determining the frequency of beta cell labelling in aldehyde-thionin stained radioautographs. Although the addition of D-glucose to the control medium resulted in a concentration-dependent increase in both insulin release and beta cell replication, the sensitivity of these two processes to glucose differed. Insulin release was stimulated by a 2.75 mM elevation in the D-glucose concentration of the control medium, while an elevation of 11 mM D-glucose was required to increase the frequency of beta cell replication. Moreover, while insulin release was maximally stimulated by an 11 mM elevation in the concentration of D-glucose, the frequency of replication continued to rise as the concentration of D-glucose was further increased. The specificity of these responses to D-glucose was demonstrated by the inability of 11 mM L-glucose or 11 mM 3-O-methyl-D-glucose to stimulate beta cell replication. D-mannose and D-fructose were less potent insulin secretagogues than D-glucose on an equimolar basis and neither compound enhanced beta cell replication at a concentration of 11 mM. However, higher concentrations of D-mannose (16.5 and 22 mM) enhanced beta cell replication, while comparable concentrations of D-fructose did not. These results indicate that the sensitivity of insulin release and beta cell replication to D-glucose differ, and that in addition to D-glucose, D-mannose is also capable of stimulating beta cell replication.