HYDROLYSIS OF HEXOSE PENTAACETATE ESTERS IN RAT PANCREATIC-ISLETS

The pentaacetate esters of selected hexoses were recently found to sti mulate insulin release. The kinetics of their hydrolysis was now inves tigated in both rat pancreatic islet homogenates and intact islets. In islet homogenates, the hydrolysis of alpha-D-glucose pentaacetate, as judged from the measurement of acetate production, displayed a pH opt imum of 7.4 and a K-m for the ester of 0.95 mM. At pH 7.4, the reactio n velocity was about 5 times higher than the rate of alpha-D-glucose p entaacetate hydrolysis by intact islets, as judged from the ester-indu ced increase in the acetate content of both the islet and surrounding incubation medium. Comparable results were obtained in intact islets e xposed to either beta-L-glucose pentaacetate or beta-D-galactose penta acetate. The ester content of the islets after 120 min incubation was close to 0.1 nmol/islet, yielding an apparent intracellular concentrat ion at least one order of magnitude higher than the extracellular conc entration (1.7 mM). These findings indicate that hexose esters that ei ther stimulate insulin release or fail to do so are equally well taken up and hydrolyzed by islet cells. They are compatible, therefore, wit h the view that the insulinotropic action of some of these esters may be favored by the catabolism of their hexose moiety, although some oth er mechanisms for stimulation of insulin release must be operative in the case of beta-L-glucose pentaacetate. (C) 1998 Elsevier Science B.V . All rights reserved.