PANCREATIC BETA-CELL REPLICATION - EFFECTS OF HEXOSE SUGARS

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, 3-0-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 labeling 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 2 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. 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 3-0-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. Higher concentrations of D-mannose (16.5 and 22 mM) enhanced .beta. cell replication, while comparable concentration of D-fructose did not. The sensitivity of insulin release and .beta. cell replication to D-glucose probably differ, and in addition to D-glucose, D-mannose is probably also capable of stimulating .beta. cell replication.