Effects of D-mannoheptose and D-glycero-D-gulo-heptose upon D-glucose metabolism and insulinotropic action in rat pancreatic islets and D-glucose phosphorylation by hexokinase isoenzymes: Comparison with D-mannoheptulose

The possible use of D-mannoheptose or D-glycero-D-gulo-heptose as substitut e of D-mannoheptulose for specific inhibition of D-glucose phosphorylation, metabolism and insulinotropic action was investigated in the present study . The two aldoheptoses failed to duplicate the effect of D-mannoheptulose u pon the phosphorylation of D-glucose by yeast hexokinase, bovine heart hexo kinase or human B-cell glucokinase. They were poorly phosphorylated by the low-K-m hexokinase isoenzymes or liver B-cell glucokinase. D-mannoheptose f ailed to reproduce the inhibitory action of D-mannoheptulose upon D-glucose metabolism by isolated rat pancreatic islets. Whilst D-glycero-D-gulo-hept ose failed to affect glucose-induced insulin release, D-mannoheptose slight ly enhanced glucose-induced insulin release when tested at low concentratio ns (0.75-1.5 mM) and progressively decreased insulin output at higher conce ntration (3.0-20.0 mM) in islets exposed to a high (16.7 mM), but not physi ological (8.3 mM), concentration of D-glucose. D-mannoheptose, however, als o caused a modest inhibition of insulin release evoked by 2-ketoisocaproate . It is concluded, therefore, that neither D-mannoheptose nor D-glycero-D-g uloheptose can be considered as suitable substitutes of D-mannoheptulose.