INSULINOTROPIC ACTION OF ALPHA-D-GLUCOSE PENTAACETATE - FUNCTIONAL-ASPECTS

The functional determinants of the insulinotropic action of alpha-D-gl ucose pentaacetate were investigated in rat pancreatic islets. The est er mimicked the effect of nutrient secretagogues by recruiting individ ual B cells into an active secretory state, stimulating proinsulin bio synthesis, inhibiting Rb-86 outflow, and augmenting Ca-45 efflux from prelabeled islets. The secretory response to the ester was suppressed in the absence of Ca2+ and potentiated by theophylline or cytochalasin B. The generation of acetate from the ester apparently played a small role in its insulinotropic action. Thus acetate, methyl acetate, ethy l acetate, alpha-D-galactose pentaacetate, and beta-D-galactose pentaa cetate all failed to stimulate insulin release. The secretory response to alpha-D-glucose pentaacetate was reproduced by beta-D-glucose pent aacetate and, to a lesser extent, by beta-L-glucose pentaacetate. It d iffered from that evoked by unesterified D-glucose by its resistance t o 3-O-methyl-D-glucose, D-mannoheptulose, and 2-deoxy-D-glucose. It is concluded that the insulinotropic action of alpha-D-glucose pentaacet ate, although linked to the generation of the hexose from its ester, e ntails a coupling mechanism that is not identical to that currently im plied in the process of glucose-induced insulin release.