Evidence for dissociation of gluconeogenesis stimulated by non-esterified fatty acids and changes in fructose 2,6-bisphosphate in cultured rat hepatocytes

Author:

Clore J N1,Stillman J S1,Helm S T1,Blackard W G1

Affiliation:

1. Medical College of Virginia/Virginia Commonwealth University, Richmond VA 23298, U.S.A.

Abstract

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.

Publisher

Portland Press Ltd.

Subject

Cell Biology,Molecular Biology,Biochemistry

Cited by 3 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Changes in Fructose-Induced Production of Glucose in the Rat Liver Following Partial Hepatectomy;Archives of Biochemistry and Biophysics;1999-11

2. Alterations of plasma lactate and glucose metabolism in obese children;American Journal of Physiology-Endocrinology and Metabolism;1996-11-01

3. The effect of changing dietary fat and carbohydrate on the enzymes of amino acid metabolism;The Journal of Nutritional Biochemistry;1995-08

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