A possible role for glucose metabolites in the regulation of inositol-1,4,5-trisphosphate 5-phosphomonoesterase activity in pancreatic islets.
Rat pancreatic islets demonstrate inositol-1,4,5-trisphosphate 5-phosphomonoesterase activity which is 3 times higher than that in the exocrine pancreas. This enzyme has several features in common with the erythrocyte and hepatocyte enzymes: it is located primarily in the plasma membrane, it has a similar Km for inositol trisphosphate (IP3) (16 microM), and it requires Mg2+. The activity of the islet enzyme is inhibited by several diphosphorylated glucose metabolites: 2,3-bisphosphoglycerate, fructose 1,6-bisphosphate, fructose 2,6-bisphosphate, and glucose 1,6-bisphosphate. Monophosphorylated and unphosphorylated metabolites have little or no effect on its activity. Several reports show that stimulation of islets with glucose raises the concentrations of various glucose metabolites including fructose 1,6-bisphosphate, glucose 1,6-bisphosphate, and 2,3-bisphosphoglycerate to concentrations that are in the range that inhibit the islet inositol-1,4,5-trisphosphate 5-phosphomonoesterase. Other reports show that IP3 mobilizes calcium when added to permeabilized insulin-secreting cells. It is possible that the increase in cytosolic calcium known to occur during glucose-induced insulin secretion may be sustained in part by higher IP3 levels resulting from the inhibition of inositol-1,4,5-trisphosphate 5-phosphomonoesterase by some of the diphosphorylated glucose metabolites.
D019794:2,3-Diphosphoglycerate; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004163:Diphosphoglyceric Acids / Q000378:metabolism; D005635:Fructosediphosphates / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D019298:Glucose-6-Phosphate / Q000031:analogs & derivatives*; D005958:Glucosephosphates / Q000378:metabolism; D000072181:Inositol Polyphosphate 5-Phosphatases; D007515:Islets of Langerhans / Q000201:enzymology*; D007700:Kinetics; D008274:Magnesium / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D051381:Rats
D004163:Diphosphoglyceric Acids; D005635:Fructosediphosphates; D005958:Glucosephosphates; D019794:2,3-Diphosphoglycerate; D019298:Glucose-6-Phosphate; C027652:fructose 2,6-diphosphate; C016473:glucose-1,6-bisphosphate; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases; D008274:Magnesium; D005947:Glucose; C029063:fructose-1,6-diphosphate; D002118:Calcium