Involvement of PI 3-kinase and activated ERK in facilitating insulin-stimulated triacylglycerol synthesis in hepatocytes.
Triacylglycerol synthesis was studied in hepatocytes isolated from fasted/refed rats by EDTA perfusion. Insulin induced a 1.5-fold increase in glucose incorporation into triacylglycerol. Insulin-stimulated triacylglycerol synthesis and insulin-stimulated protein kinase B/Akt activity were inhibited by the phosphatidylinositol 3-kinase inhibitors wortmannin and LY 294002, and the mitogen-activated protein kinase kinase inhibitor PD 98059. Inhibition of p70 ribosomal protein-S6 kinase with rapamycin was without effect. Insulin-stimulated pyruvate dehydrogenase activity was abolished by phosphatidylinositol 3-kinase inhibitors. No effect of insulin on acetyl CoA carboxylase activity was observed.
Carlsen
J
J
Department of Medical Biochemistry and Genetics, The Panum Institute, University of Copenhagen, Denmark. jbc@imbg.ku.dk
Christiansen
K
K
Grunnet
N
N
Vinten
J
J
D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005419:Flavonoids / Q000037:antagonists & inhibitors; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019893:Ribosomal Protein S6 Kinases / Q000037:antagonists & inhibitors; D020123:Sirolimus / Q000494:pharmacology; D014280:Triglycerides / Q000096:biosynthesis*; D000077191:Wortmannin
D000103:Acetyl-CoA Carboxylase; D000730:Androstadienes; D002867:Chromones; D004791:Enzyme Inhibitors; D005419:Flavonoids; D005947:Glucose; D007328:Insulin; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D011768:Pyruvate Dehydrogenase Complex; D019893:Ribosomal Protein S6 Kinases; D020123:Sirolimus; D014280:Triglycerides; D000077191:Wortmannin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C494920:Akt1 protein, rat; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one