Inhibition of glycogenolysis by 2,5-anhydro-D-mannitol in isolated rat hepatocytes.
2,5-Anhydro-D-mannitol, an analog of D-fructofuranose, inhibited basal and glucagon-stimulated glycogenolysis and glucose production in hepatocytes isolated from fed rats. Glucose formation from galactose was unaffected by the inhibitor. 2,5-Anhydro-D-mannitol-1-phosphate inhibits phosphorylase alpha with a Ki value of 2.4 mM. This same phosphorylated metabolite accumulates to the extent of 9.2 mumol/g wet wt in treated hepatocytes suggesting that phosphorolysis is the locus of the inhibition of glucose production from glycogen. Our results suggest that 2,5-anhydro-D-mannitol can be used to produce a model of hereditary fructose intolerance and that it merits further study as a hypoglycemic agent.
D000818:Animals; D005934:Glucagon / Q000494:pharmacology; D005947:Glucose / Q000096:biosynthesis; D006003:Glycogen / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008353:Mannitol / Q000031:analogs & derivatives* / Q000494:pharmacology; D008355:Mannitol Phosphates / Q000494:pharmacology; D010762:Phosphorylase a / Q000037:antagonists & inhibitors; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains
D008355:Mannitol Phosphates; D008353:Mannitol; C031765:2,5-anhydromannitol; C040222:2,5-anhydromannitol 1-phosphate; D006003:Glycogen; D005934:Glucagon; D010762:Phosphorylase a; D005947:Glucose