Inhibition of glucose-stimulated insulin release by pseudo-alpha-DL-glucose as a glucokinase inhibitor.
Pseudo-alpha- and pseudo-beta-DL-glucose, the isomers of 5-hydroxymethyl-1,2,3,4-cyclohexanetetrol with alpha-gluco and beta-gluco configurations, were used as synthetic analogs of glucose anomers to study the mechanism of glucose-stimulated insulin release by pancreatic islets. Neither isomer was phosphorylated by liver glucokinase nor stimulated insulin release from islets. Incubation of islets with pseudo-alpha-DL-glucose resulted in a considerable accumulation of the glucose analog, probably the D form, in islets. The alpha-isomer, but not the beta-isomer, inhibited both glucose-stimulated insulin release (44% inhibition at 20 mM) and islet glucokinase activity (36% inhibition at 20 mM) in a concentration-dependent manner and to a comparable degree. These results strongly suggest that the inhibition of glucose-stimulated insulin release by pseudo-alpha-DL-glucose is due to the inhibition of islet glucokinase by the glucose analog, providing additional evidence for the essential role of islet glucokinase in glucose-stimulated insulin release.
D000818:Animals; D005941:Glucokinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005947:Glucose / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D006593:Hexokinase / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D007328:Insulin; C048030:5-hydroxymethyl-1,2,3,4-cyclohexanetetrol; D006593:Hexokinase; D005941:Glucokinase; D005947:Glucose