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 substitute 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 upon the phosphorylation of D-glucose by yeast hexokinase, bovine heart hexokinase or human B-cell glucokinase. They were poorly phosphorylated by the low-Km hexokinase isoenzymes or liver B-cell glucokinase. D-mannoheptose failed to reproduce the inhibitory action of D-mannoheptulose upon D-glucose metabolism by isolated rat pancreatic islets. Whilst D-glycero-D-gulo-heptose failed to affect glucose-induced insulin release, D-mannoheptose slightly enhanced glucose-induced insulin release when tested at low concentrations (0.75-1.5 mM) and progressively decreased insulin output at higher concentration (3. 0-20.0 mM) in islets exposed to a high (16.7 mM), but not physiological (8.3 mM), concentration of D-glucose. D-mannoheptose, however, also caused a modest inhibition of insulin release evoked by 2-ketoisocaproate. It is concluded, therefore, that neither D-mannoheptose nor D-glycero-D-guloheptose can be considered as suitable substitutes of D-mannoheptulose.
Courtois
P
P
Laboratory of Experimental Medicine, Brussels Free University, B-1070 Brussels, Belgium.
Sener
A
A
Malaisse
W J
WJ
D000818:Animals; D002417:Cattle; D005260:Female; D005947:Glucose / Q000378:metabolism*; D005990:Glycerol / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D006539:Heptoses / Q000378:metabolism / Q000494:pharmacology*; D006593:Hexokinase / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects* / Q000502:physiology; D007527:Isoenzymes / Q000378:metabolism; D008356:Mannoheptulose / Q000378:metabolism / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats
D006539:Heptoses; D007328:Insulin; D007527:Isoenzymes; C413546:glycero-gulo-heptose; C413547:mannoheptose; D008356:Mannoheptulose; D006593:Hexokinase; D005947:Glucose; D005990:Glycerol