Evidence for dissociation of gluconeogenesis stimulated by non-esterified fatty acids and changes in fructose 2,6-bisphosphate in cultured rat hepatocytes.
In order to examine the role of fructose 2,6-bisphosphate (Fru-2,6-P2) in non-esterified-fatty-acid-stimulated gluconeogenesis, Fru-2,6-P2 levels were measured in cultured rat hepatocytes under conditions mimicking the fasted state. After addition of either 1.5 mM-palmitate or 10 nM-glucagon, [U-14C]lactate incorporation into glucose increased 2-fold, but only glucagon suppressed Fru-2,6-P2. Prevention of palmitate oxidation with a carnitine palmitoyltransferase-I inhibitor (2-bromopalmitate) diminished glucose production and Fru-2,6-P2 levels. Addition of exogenous glucose to the media increased Fru-2,6-P2 in a dose-related manner, which was further augmented by addition of palmitate. When Fru-2,6-P2 levels were examined in cells cultured under conditions mimicking the fed state (significantly higher basal Fru-2,6-P2 levels and lower glucose production), palmitate oxidation was associated with a significant fall in Fru-2,6-P2. In conclusion, the present studies have demonstrated a dissociation between fatty-acid-stimulated gluconeogenesis and changes in Fru-2,6-P2 in cultured rat hepatocytes. Further experiments suggest that the accumulation of intracellular hexose 6-phosphate as a result of fatty-acid-stimulated gluconeogenesis masks a putative inhibitory effect of fatty acids on Fru-2,6-P2 concentrations.
Clore
J N
JN
Medical College of Virginia/Virginia Commonwealth University, Richmond 23298.
Stillman
J S
JS
Helm
S T
ST
Blackard
W G
WG
D000818:Animals; D002210:Caprylates / Q000494:pharmacology; D002478:Cells, Cultured; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D005635:Fructosediphosphates / Q000378:metabolism*; D005934:Glucagon / Q000494:pharmacology; D005943:Gluconeogenesis / Q000187:drug effects*; D007328:Insulin / Q000494:pharmacology; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010168:Palmitates / Q000494:pharmacology; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D002210:Caprylates; D005230:Fatty Acids, Nonesterified; D005635:Fructosediphosphates; D007328:Insulin; D007773:Lactates; D010168:Palmitates; D010169:Palmitic Acids; C022776:2-bromopalmitate; D019308:Palmitic Acid; D019344:Lactic Acid; C027652:fructose 2,6-diphosphate; D005934:Glucagon; C031492:octanoic acid