Altered fluxes responsible for suppression of hepatic glucose
production and apparent gluconeogenesis by exogenous glucose in
previously fasted rats.
Hellerstein, Marc K., Richard A. Neese, Jean-Marc Schwarz, Scott
Turner, Dennis Faix, Kenneth Wu.
Department of Nutritional Sciences, 309 Morgan Hall, University of
California, Berkeley, CA 94720-3104, Division of Endocrinology and
Medicine, Department of Medicine, San Francisco General Hospital,
University of California, 1001 Potrero Avenue, San Francisco, CA
94110
APStracts 3:0192E, 1996.
The net release of glucose from the liver, or hepatic glucose
production [HGP], and apparent gluconeogenesis (GNG) are reduced by
exogenous glucose. We investigated the changes in metabolic fluxes
responsible. Flux through the hepatic GNG pathway was quantified by
mass isotopomer distribution analysis (MIDA) from [2-13C]-glycerol.
Unidirectional flux across hepatic glucose 6-phosphatase (G6P'ase),
or total hepatic glucose output (THGO), and hepatic glucose cycling
(HGC) were also measured, by using glucuronate (GlcUA) to correct for
G6P labeling. Infusion of glucose (15-30 mg/kg/min iv) to 24-hr
fasted rats caused two important metabolic alterations. First was a
significant increase in hepatic glucose uptake and HGC: more than 60%
of THGO was from HGC. Second, although flux through hepatic G6P
increased (from 15.7 to 17.7 - 22.7 mg/kg/min) the partitioning of
G6P flux changed markedly (from 30-35% to 55-60% entering UDP-glc,
p<0.01). Total flux through GNG pathway remained active during
iv glucose but increased partitioning into UDP-glc lowered GNG flux
plasma glucose by 50%. In summary, the suppression of HGP and GNG
flux into glucose is not primarily due to reduced carbon flow through
hepatic G6P'ase or the hepatic GNG pathway. THGO persists but hepatic
G6P is derived increasingly from plasma glucose, and flow through GNG
persists but the partitioning coefficient of G6P into UDP-Glc
doubles. These adjustments permit net HGP to fall despite increased
total production of hepatic G6P during administration of glucose.
Received 11 March 1996; accepted in final form 20 August 1996.
APS Manuscript Number E118-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 7 October 1996