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Am J Physiol Endocrinol Metab 293: E1352-E1357, 2007. First published August 28, 2007; doi:10.1152/ajpendo.00394.2007
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Glyceroneogenesis and the supply of glycerol-3-phosphate for glyceride-glycerol synthesis in liver slices of fasted and diabetic rats

Maria Emilia Soares Martins-Santos, Valéria Ernestânia Chaves, Danúbia Frasson, Renata Polessi Boschini, Maria Antonieta Rissato Garófalo, Isis do Carmo Kettelhut, and Renato Hélios Migliorini

Departments of Biochemistry-Immunology and Physiology, School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil

Submitted 21 June 2007 ; accepted in final form 24 August 2007

The pathways of glycerol-3-phosphate (G3P) generation for glyceride synthesis were examined in precision-cut liver slices of fasted and diabetic rats. The incorporation of 5 mM [U-14C]glucose into glyceride-glycerol, used to evaluate G3P generation via glycolysis, was reduced by ~26–36% in liver slices of fasted and diabetic rats. The glycolytic flux was reduced by ~60% in both groups. The incorporation of 1.0 mM [2-14C]pyruvate into glyceride-glycerol (glyceroneogenesis) increased ~50% and ~36% in slices of fasted and diabetic rats, respectively, which also showed a two-fold increase in the activity phosphoenolpyruvate carboxykinase. The increased incorporation of 1.0 mM [2-14C]pyruvate into glyceride-glycerol by slices of fasted rats was not affected by the addition of 5 mM glucose to the incubation medium. The activity of glycerokinase and the incorporation of 1 mM [U-14C]glycerol into glyceride-glycerol, evaluators of G3P formation by direct glycerol phosphorylation, did not differ significantly from controls in slices of the two experimental groups. Rates of incorporation of 1 mM [2-14C]pyruvate and [U-14C]glycerol into glucose of incubation medium (gluconeogenesis) were ~140 and ~20% higher in fasted and diabetic slices than in control slices. It could be estimated that glyceroneogenesis by liver slices of fasted rats contributed with ~20% of G3P generated for glyceride-glycerol synthesis, the glycolytic pathway with ~5%, and direct phosphorylation of glycerol by glycerokinase with ~75%. Pyruvate contributed with 54% and glycerol with 46% of gluconeogenesis. The present data indicate that glyceroneogenesis has a significant participation in the generation of G3P needed for the increased glyceride-glycerol synthesis in liver during fasting and diabetes.

phosphoenolpyruvate carboxykinase; glycerokinase; [U-14C]glucose; [2-14C]pyruvate; [U-14C]glycerol; gluconeogenesis


Address for reprint requests and other correspondence: R. H. Migliorini, Dept. of Biochemistry and Immunology, School of Medicine, USP. 14049-900 Ribeirão Preto, São Paulo, Brazil (e-mail: rhmiglio{at}fmrp.usp.br)






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