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 that involved in the recognition of bitter agents by taste buds may also be operative. In the present study, the secretory response of rat isolated pancreatic islets to alpha-D-glucose pentaacetate (1.7 mM) was found to be preserved, except in the absence of any other exogenous nutrient, when the extracellular 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 inhibited both basal and D-glucose- or L-leucine-stimulated insulin output. These findings are interpreted to support a dual mode of action of alpha-D-glucose pentaacetate upon insulin secretion, a lowering of extracellular pH revealing a negative component of the islet B-cells functional response to such a monosaccharide ester.