title: Inhibition of phosphofructokinase activity in pancreatic islets in phosphate depletion.
abstract: Phosphate depletion (PD) causes marked and significant reduction in glucose-induced insulin secretion by pancreatic islets. Certain data suggest that a defect in glucose metabolism, prior to the generation of glyceraldehyde-3-phosphate, by the islets is partly responsible for the impairment in insulin secretion. Phosphofructokinase-1 (PFK-1) is the enzyme that facilitates the conversion of fructose-6-phosphate to fructose-1,2-bisphosphate, a step in the glycolytic pathway that precedes the production of triose phosphates. It is, therefore, possible that PD impairs the activity of this enzyme and contributes to the defect in glucose metabolism by pancreatic islets. We studied the Vmax and Km of PFK-1 for fructose-6-phosphate in islets obtained from PD rats and pair-weighed (PW) animals fed the PD and normal diets, respectively, for 6 weeks. PD did not affect the Vmax of PFK-1 but the Km of the enzyme for fructose-6-phosphate was significantly (p less than 0.01) higher in PD (0.364 +/- 0.056 mM) than in PW rats (0.244 +/- 0.019 mM). The data demonstrate that in PD (a) the affinity of PFK-1 for its substrate fructose-6-phosphate is reduced; (b) the combination of normal Vmax and high Km points toward the presence of a negative allosteric effector, and (c) the change in the activity of PFK-1 contributes to the defect in glucose metabolism by the pancreatic islets.
authors.affiliation: Division of Nephrology, University of Southern California School of Medicine, Los Angeles.
authors.forename: A F
authors.initials: AF
authors.lastname: Perna
authors.forename: G Z
authors.initials: GZ
authors.lastname: Fadda
authors.forename: S G
authors.initials: SG
authors.lastname: Massry
mesh_terms: D000818:Animals; D002118:Calcium / Q000097:blood; D007515:Islets of Langerhans / Q000201:enzymology*; D008297:Male; D010710:Phosphates / Q000172:deficiency*; D010732:Phosphofructokinase-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010758:Phosphorus / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D010710:Phosphates; D010758:Phosphorus; D010732:Phosphofructokinase-1; D002118:Calcium