Biochem. J. (2007) 401
(465473) (Printed in Great Britain)
Glutamine gluconeogenesis in the small intestine of 72 h-fasted adult rats is undetectable
Guy MARTIN, Bernard FERRIER, Agnès CONJARD, Mireille MARTIN, Rémi NAZARET, Michelle BOGHOSSIAN, Fadi SAADÉ, Claire MANCUSO, Daniel DUROZARD and Gabriel BAVEREL1
Institut National de la Santé et de la Recherche Médicale, UMR 499, Animet, Faculté de Médecine RTH Laennec, Université Lyon 1, Rue G. Paradin, 69372 Lyon Cedex 08, France
Recent reports have indicated that 4872 h of fasting, Type 1 diabetes and high-protein feeding induce gluconeogenesis in the small intestine of adult rats in vivo. Since this would (i) represent a dramatic revision of the prevailing view that only the liver and the kidneys are gluconeogenic and (ii) have major consequences in the metabolism, nutrition and diabetes fields, we have thoroughly re-examined this question in the situation reported to induce the highest rate of gluconeogenesis. For this, metabolically viable small intestinal segments from 72 h-fasted adult rats were incubated with [3-13C]glutamine as substrate. After incubation, substrate utilization and product accumulation were measured by enzymatic and NMR spectroscopic methods. Although the segments utilized [13C]glutamine at high rates and accumulated 13C-labelled products linearly for 30 min in vitro, no substantial glucose synthesis could be detected. This was not due to the re-utilization of [13C]glucose initially synthesized from [13C]glutamine. Arteriovenous metabolite concentration difference measurements across the portal vein-drained viscera of 72 h-fasted Wistar and SpragueDawley rats clearly indicated that glutamine, the main if not the only gluconeogenic precursor taken up, could not give rise to detectable glucose production in vivo. Therefore we challenge the view that the small intestine of the adult rat is a gluconeogenic organ.
Key words: gluconeogenesis, glucose synthesis, glutamine metabolism, ketone body, NMR spectroscopy, small intestine.
Abbreviations used: PEPCK, phosphoenolpyruvate carboxykinase.
1To whom correspondence should be addressed (email baverel@sante.univ-lyon1.fr).
Received 28 July 2006/19 September 2006; accepted 27 September 2006
Published as BJ Immediate Publication 27 September 2006, doi:10.1042/BJ20061148
The Biochemical Society, London ©2007