Kinetics and specificity of human B-cell glucokinase: relevance to hexose-induced insulin release.
The present study reevaluates the relevance of human B-cell glucokinase activity to the process of hexose-induced insulin release. Taking into account a phenomenon of positive cooperativity (Hill number: 1.34), the Km of the enzyme for glucose ( < or = 5.1 mM) was lower than the concentration of the hexose required to cause half-maximal stimulation of insulin release in intact islets. Likewise, there were obvious discrepancies between the kinetics of glucose, mannose and fructose phosphorylation by B-cell glucokinase, e.g. in terms of maximal velocity, and the secretory and metabolic responses to these hexoses in intact islets. Glucose 6-phosphate decreased, modestly but significantly, B-cell glucokinase activity, such an inhibitory action being of the non-competitive type. Mannoheptulose caused competitive inhibition of B-cell glucokinase. It is concluded that the intrinsic catalytic properties of B-cell glucokinase cannot fully account for the concentration dependency and sugar specificity of the secretory response to D-glucose or other hexoses in pancreatic islets.
Sener
A
A
Laboratory of Experimental Medicine, Brussels Free University, Belgium.
Malaisse
W J
WJ
D002478:Cells, Cultured; D005941:Glucokinase / Q000378:metabolism*; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000494:pharmacology; D006601:Hexoses / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000201:enzymology* / Q000378:metabolism; D007700:Kinetics; D008356:Mannoheptulose / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D013379:Substrate Specificity
D005958:Glucosephosphates; D006601:Hexoses; D007328:Insulin; D019298:Glucose-6-Phosphate; D008356:Mannoheptulose; D005941:Glucokinase