Email: ranar@stjohns.edu
It is widely recognized that insulin output of pancreas is
regulated by the concentration of blood sugar. However, in spite of
the revolutionary advances in diabetes care, the molecular
mechanism underlying the coupling of blood glucose rise to release
of insulin release remains obscure. Recent evidence from this
laboratory has implicated glucose metabolism and nitric oxide as
important mediators and modulators of insulin release. Two glucose
metabolites, namely, 2,3-bisphosphoglycerate and
fructose-1,6-bisphosphate, have been shown to mobilize calcium from
intracellular stores in permeabilized cells. This
calcium-mobilizing activity appears to result from an interaction
of these metabolites with the inositol trisphosphate receptor. The
focus of current studies is to manipulate intracellular
concentrations of glucose metabolites using liposomes loaded with
test metabolites. A second line of research has concentrated on
identifying role of nitric oxide in the modulation of
glucose-induced insulin release. We have shown that nitric oxide
donors potentiate glucose-induced insulin release, whereas nitric
oxide scavengers have the opposite effect. Since nitric oxide alone
does not stimulate insulin release, effect of nitric oxide appears
to be directed at the level of modulation rather than initiation of
insulin release. The precise biochemical steps involved in nitric
oxide effect, however, are not clearly understood. Current work
aims to test specific hypotheses to determine if nitric oxide
exerts its modulatory effect by influencing glucose-induced
intracellular calcium signaling, either directly by releasing
calcium from intracellular stores or by stimulating production of
other second messengers, such as cyclic-GMP. The novel aspect of
this research is that ordinary metabolites of glucose may have
extraordinary effects on signal transduction pathways.
Recent publications
Lubell, A., Chandarana, H., Rana, R. S. (1999). Glycolytic
metabolites and intracellular signaling in the pancreatic beta
cell. Archives of Biochemistry and Biophysics, 364, 178-184.
Ding, Y., Rana, R. S. (1998). Nitric oxide does not initiate but
potentiates glucose-induced insulin secretion in pancreatic beta
cells. Biochem. Biophys. Res. Commun., 251: 699-703.