Hexose metabolism in pancreatic islets. Inhibition of hexokinase.
In islet homogenates, hexokinase-like activity (Km 0.05 mM; Vmax. 1.5 pmol/min per islet) accounts for the major fraction of glucose phosphorylation. Yet the rate of glycolysis in intact islets incubated at low glucose concentrations (e.g. 1.7 mM) sufficient to saturate hexokinase only represents a minor fraction of the glycolytic rate observed at higher glucose concentrations. This apparent discrepancy between enzymic and metabolic data may be attributable, in part at least, to inhibition of hexokinase in intact islets. Hexokinase, which is present in both islet and purified B-cell homogenates, is indeed inhibited by glucose 6-phosphate (Ki 0.13 mM) and glucose 1,6-bisphosphate (Ki approx. 0.2 mM), but not by fructose 2,6-bisphosphate. In intact islets, the steady-state content of glucose 6-phosphate (0.26-0.79 pmol/islet) and glucose 1,6-bisphosphate (5-48 fmol/islet) increases, in a biphasic manner, at increasing concentrations of extracellular glucose (up to 27.8 mM). From these measurements and the intracellular space of the islets, it was estimated that the rate of glucose phosphorylation as catalysed by hexokinase represents, in intact islets, no more than 12-24% of its value in islet homogenates.
D000818:Animals; D005947:Glucose / Q000378:metabolism; D019298:Glucose-6-Phosphate / Q000031:analogs & derivatives; D005958:Glucosephosphates / Q000378:metabolism; D006593:Hexokinase / Q000037:antagonists & inhibitors*; D006601:Hexoses / Q000378:metabolism*; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000201:enzymology*; D007700:Kinetics; D008358:Mannose / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats
D005958:Glucosephosphates; D006601:Hexoses; D019298:Glucose-6-Phosphate; C016473:glucose-1,6-bisphosphate; D006593:Hexokinase; D005947:Glucose; D008358:Mannose