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 now investigated whether they mimic the effect of nutrient secretagogues to cause a phosphate flush and activation of phospholipase C in isolated islets. For this purpose, rat pancreatic islets were prelabelled with either [(32)P]orthophosphate or myo-[2-(3)H]inositol and placed in a perifusion chamber. In the absence of any other exogenous nutrient, the administration of alpha-D-glucose pentaacetate (1.7 mM) from 46 to 70 min of perifusion increased, after an initial transient fall, both 32P and 3H fractional outflow rates and stimulated insulin release from the perifused islets. No secondary rise in either (32)P or (3)H outflow and no sizeable stimulation of insulin release was observed, however, in response to Beta-L-glucose pentaacetate (also 1.7 mM). These findings are consistent with the view that the insulinotropic action of alpha-D-glucose pentaacetate entails a nutrient-like component leading to the occurrence of both a phosphate flush and hydrolysis of phosphoinositides. This is not the case, however, for Beta-L-glucose pentaacetate. The latter ester might act directly on a yet unidentified receptor, the early secretory response to alpha-D-glucose pentaacetate also apparently involving such a direct effect of the ester itself.

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