Permissive action of triiodothyronine on the long-term increase of glycolysis by insulin in cultured rat hepatocytes.
The long-term influence of triiodothyronine (T3) and insulin on glycolysis, some glycolytic/gluconeogenic enzymes and insulin responsiveness and sensitivity was investigated in rat hepatocytes cultured for 48 h without T3, with 10 microM T3, with 10nM insulin and with insulin plus T3. From 48 h-51 h basal glycolysis ([14C]lactate formation from [14C]glucose) was measured in the absence and short-term insulin-stimulated glycolysis in the presence of 100 nM insulin. 1) T3 addition for 48 h had no significant influence on basal or on insulin-stimulated glycolysis. 2) Insulin addition for 48 h increased basal glycolysis to 300%, and insulin-stimulated glycolysis to 160%. 3) T3 plus insulin addition for 48 h elevated basal glycolysis to 560% and insulin-stimulated glycolysis to 230%. 4) The 48-h treatment with T3 did not change glucokinase (GK) and pyruvate kinase (PK) activity, yet it increased phosphoenol-pyruvate carboxykinase (PEPCK) activity to 150%. 5) The 48-h treatment with insulin as well as T3 plus insulin enhanced GK to 200% and PK to 140% and decreased PEPCK to 65%. 6) The long-term effect of T3 on glycolysis was maximal at initial concentrations of 100 nM. 7) The long-term treatment with T3 did not alter the short-term responsiveness or sensitivity of glycolysis for insulin, neither in cells from euthyroid nor from hypothyroid rats. The present results allow the conclusion that T3 had a permissive effect on the long-term increase of glycolysis by insulin, and that T3 exerted this function by altering neither the cellular content of key enzymes nor the short-term insulin responsiveness and sensitivity.
Rosa
J
J
Institut für Biochemie, Fachbereich Medizin, Universität Göttingen.
Probst
I
I
Jungermann
K
K
D000818:Animals; D002478:Cells, Cultured; D004347:Drug Interactions; D005941:Glucokinase / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects*; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010730:Phosphoenolpyruvate Carboxylase / Q000378:metabolism; D011770:Pyruvate Kinase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D014284:Triiodothyronine / Q000494:pharmacology*
D007328:Insulin; D014284:Triiodothyronine; D005941:Glucokinase; D011770:Pyruvate Kinase; D010730:Phosphoenolpyruvate Carboxylase