Effects of extracellular pH upon the insulinotropic action of alpha-D-glucose pentaacetate

The pentaacetate ester of alpha-D-glucose was recently introduced as a new insulin secretagogue. Its insulinotropic action appears mainly attributable to the catabolism of its hexose moiety in islet cells, but a direct effect of the ester itself upon a receptor apparently displaying analogy with tha t involved in the recognition of bitter agents by taste buds may also be op erative. In the present study, the secretory response of rat isolated pancr eatic islets to alpha-D-glucose pentaacetate (1.7 mM) was found to be prese rved, except in the absence of any other exogenous nutrient, when the extra cellular pH was raised from about 7.4 to 8.0. Inversely, however, when the extracellular pH was lowered to about 7.0, alpha-D-glucose pentaacetate inh ibited both basal and D-glucose- or L-leucine-stimulated insulin output. Th ese findings are interpreted to support a dual mode of action of alpha-D-gl ucose pentaacetate upon insulin secretion, a lowering of extracellular pH r evealing a negative component of the islet B-cells functional response to s uch a monosaccharide ester.