Insulin stimulated glycogen synthesis in isolated rat hepatocytes: effect of protein kinase inhibitors.
Glycogen synthesis was studied in rat hepatocytes isolated by EDTA perfusion. Insulin induced a one and a half to twofold increase in glucose incorporation into glycogen. Insulin stimulated glycogen synthesis was inhibited by the phosphatidylinositol 3-kinase inhibitors wortmannin (IC50 approximately 40 nM) and LY 294002 (IC50 approximately 20 microM) and the mitogen-activated protein kinase kinase inhibitor PD 98059 (IC50 approximately 40 microM). Wortmannin was without appreciable effect on non-insulin stimulated glycogen synthesis, while LY 294002 and PD 98059 also inhibited the non-insulin stimulated glycogen synthesis. Rapamycin, an inhibitor of p70 ribosomal protein-S6 kinase, was without effect on glycogen synthesis regardless of insulin stimulation.
Carlsen
J
J
Department of Medical Biochemistry and Genetics, University of Copenhagen, Denmark.
Christiansen
K
K
Vinten
J
J
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002867:Chromones / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000096:biosynthesis*; D006006:Glycogen Synthase / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000201:enzymology; D020929:Mitogen-Activated Protein Kinase Kinases; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011090:Polyenes / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism; D019893:Ribosomal Protein S6 Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D020123:Sirolimus; D000077191:Wortmannin
D000730:Androstadienes; D002867:Chromones; D004791:Enzyme Inhibitors; D005419:Flavonoids; D005947:Glucose; D006003:Glycogen; D006006:Glycogen Synthase; D007004:Hypoglycemic Agents; D007328:Insulin; D020929:Mitogen-Activated Protein Kinase Kinases; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011090:Polyenes; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D011972:Receptor, Insulin; D019893:Ribosomal Protein S6 Kinases; D020123:Sirolimus; D000077191:Wortmannin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one