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

The metabolism of alpha-D-glucose pentaacetate and its positive insulinotro pic action in isolated rat pancreatic islets are both unexpectedly resistan t to D-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 investigat ed in perifused islets prelabeled with either Rb-86 Or Ca-45. At a 10 mM co ncentration, sufficient to abolish the inhibitory action of unesterified D- glucose upon 86Rb outflow, D-mannoheptulose failed to suppress the decrease in Rb-86 outflow and increase in Ca-45 efflux caused by alpha-D-glucose pe ntaacetate at normal extracellular Ca2+ concentration and also failed to pr event the decrease in both Ca-45 and insulin release provoked by the ester in the absence of extracellular Ca2+. The sole obvious effect of the heptos e was to change the early peak-shaped positive secretory response to alpha- D-glucose pentaacetate to a transient inhibition of insulin release. This c hange was observed in islets either deprived of any other exogenous nutrien t or exposed to L-leucine throughout the experiments. These findings suppor t the view that the islet functional response to alpha-D-glucose pentaaceta te is largely resistant to D-mannoheptulose. They also reinforce the concep t that the insulinotropic action of this and other monosaccharide esters in volves 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.