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

Abstract

The metabolism of alpha-D-glucose pentaacetate and its positive insulinotropic action in isolated rat pancreatic islets are both unexpectedly resistant 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 investigated in perifused islets prelabeled with either 86Rb or 45Ca. At a 10 mM concentration, sufficient to abolish the inhibitory action of unesterified D-glucose upon 86Rb outflow, D-mannoheptulose failed to suppress the decrease in 86Rb outflow and increase in 45Ca efflux caused by alpha-D-glucose pentaacetate at normal extracellular Ca2+ concentration and also failed to prevent the decrease in both 45Ca 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 alpha-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 to L-leucine throughout the experiments. These findings support the view that the islet functional response to alpha-D-glucose pentaacetate is largely resistant to D-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.