Effects of alpha-D- and beta-L-glucose pentaacetate on effluent radioactivity from pancreatic islets labelled with [P-32]phosphate and myo-[2-H-3]inositol

The anomers of both D-glucose pentaacetate and L-glucose pentaacetate were recently found to display insulinotropic potential. In order to progress in understanding the mode of action of these esters in islet cells, we have n ow investigated whether they mimic the effect of nutrient secretagogues to cause a phosphate flush and activation of phospholipase C in isolated islet s. For this purpose, rat pancreatic islets were prelabelled with either [P- 32]orthophosphate or myo-[2-H-3]inositol and placed in a perifusion chamber . In the absence of any other exogenous nutrient, the administration of alp ha-D-glucose pentaacetate (1.7 mM) from 46 to 70 min of perifusion increase d, after an initial transient fall, both P-32 and H-3 fractional outflow ra tes and stimulated insulin release from the perifused islets. No secondary rise in either P-32 or H-3 outflow and no sizeable stimulation of insulin r elease was observed, however, in response to beta-L-glucose pentaacetate (a lso 1.7 mM). These findings are consistent with the view that the insulinot ropic action of alpha-D-glucose pentaacetate entails a nutrient-like compon ent leading to the occurrence of both a phosphate flush and hydrolysis of p hosphoinositides. This is not the case, however, for beta-L-glucose pentaac etate. The latter ester might act directly on a yet unidentified receptor, the early secretory response to alpha-D-glucose pentaacetate also apparentl y involving such a direct effect of the eater itself.