Glycolytic Metabolites and Intracellular Signaling in the Pancreatic Beta Cell

Abstract

In the pathways modulating the secretion of insulin and other physiologically important molecules, the critical role played by calcium in the moment-to-moment regulation of secretory processes may be modulated by additional factors, and these factors may include the glycolytic metabolites. We studied these early glucose breakdown products for effects on calcium release and inositol 1,4,5-trisphosphate (IP3) binding to the IP3receptor in a pancreatic beta cell preparation. The physiological significance of the response was also examined in terms of the insulinotropic effects of these metabolites. In studies of calcium release from the pancreatic beta cell, the metabolite 2,3-bisphosphoglycerate (DPG) exerted a statistically significant stimulatory effect on calcium release. A lesser but nonetheless significant effect also occurred in the presence of 3-phosphoglycerate and glucose-6-phosphate. The DPG-induced effect was concentration dependent. It is likely that the effects of DPG and other glycolytic metabolites on pancreatic beta cell signaling are physiologically significant inasmuch as we were also able to demonstrate that DPG and other glycolytic metabolites promoted the release of insulin from the pancreatic beta cell.