Effect ofD-mannoheptulose upon the cationic and secretory responses to α-D-glucose pentaacetate in perifused rat pancreatic islets

The metabolism of α-D-glucose pentaacetate and its positive insulinotropic action in isolated rat pancreatic islets are both unexpectedly resistant toD-mannoheptulose, as judged from experiments conducted over 90–120 min incubation. In the present study, the possible effects of the heptose upon the immediate cationic and secretory response to the ester were investigated in perifused islets prelabeled with either86Rb or45Ca. At a 10 mM concentration, sufficient to abolish the inhibitory action of unesterifiedD-glucose upon86Rb outflow,d-mannoheptulose failed to suppress the decrease in86Rb outflow and increase in45Ca efflux caused by α-D-glucose pentaacetate at normal extracellular Ca2+ concentration and also failed to prevent the decrease in both45Ca and insulin release provoked by the ester in the absence of extracellular Ca2+. The sole obvious effect of the heptose was to change the early peak-shaped positive secretory response to α-D-glucose pentaacetate to a transient inhibition of insulin release. This change was observed in islets either deprived of any other exogenous nutrient or exposed toL-leucine throughout the experiments. These findings support the view that the islet functional response to α-D-glucose pentaacetate is largely resistant toD-mannoheptulose. They also reinforce the concept that the insulinotropic action of this and other monosaccharide esters involves a dual modality of B-cell activation, linked to both the catabolism of their carbohydrate moieties and a direct effect of the esters themselves upon a specific receptor system.