Recent studies in vivo have suggested that, in humans in the postabsorptive state, the kidneys contribute a significant fraction of systemic gluconeogenesis, and that the stimulation of renal gluconeogenesis may fully explain the increase in systemic gluconeogenesis during adrenaline infusion. Given the potential importance of human renal gluconeogenesis in various physiological and pathophysiological situations, we have conducted a study in vitro to further characterize this metabolic process and its regulation. For this, successive segments (S1, S2 and S3) of human proximal tubules were dissected and incubated with physiological concentrations of glutamine or lactate, two potential gluconeogenic substrates that are taken up by the human kidney in vivo, and glucose production was measured. The effects of adrenaline, noradrenaline and cAMP, a well established stimulator of gluconeogenesis in animal kidney tubules, were also studied in suspensions of human renal proximal tubules. The results indicate that the three successive segments have about the same capacity to synthesize glucose from glutamine; by contrast, the S2 and S3 segments synthesize more glucose from lactate than the S1 segment. In the S2 and S3 segments, lactate appears to be a better gluconeogenic precursor than glutamine. The addition of cAMP, but not of adrenaline or noradrenaline, led to the stimulation of gluconeogenesis from lactate and glutamine by human proximal tubules. These results indicate that, in the human kidney in vivo, lactate might be the main gluconeogenic precursor, and that the stimulation of renal gluconeogenesis observed in vivo upon adrenaline infusion may result from an indirect action on the renal proximal tubule.
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December 2001
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Research Article|
November 26 2001
Gluconeogenesis from glutamine and lactate in the isolated humanrenal proximal tubule: longitudinal heterogeneity and lack of response to adrenaline
Agnès CONJARD;
Agnès CONJARD
1
Laboratoire de Physiopathologie Métabolique et Rénale, Institut National de la Santé et de la Recherche Médicale, U499, Faculté de Médecine R.T.H. Laennec, rue G. Paradin, 69372 Lyon Cedex 08, France
1To whom correspondence should be addressed (e-mail [email protected]).
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Mireille MARTIN;
Mireille MARTIN
Laboratoire de Physiopathologie Métabolique et Rénale, Institut National de la Santé et de la Recherche Médicale, U499, Faculté de Médecine R.T.H. Laennec, rue G. Paradin, 69372 Lyon Cedex 08, France
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Jérôme GUITTON;
Jérôme GUITTON
Laboratoire de Physiopathologie Métabolique et Rénale, Institut National de la Santé et de la Recherche Médicale, U499, Faculté de Médecine R.T.H. Laennec, rue G. Paradin, 69372 Lyon Cedex 08, France
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Gabriel BAVEREL;
Gabriel BAVEREL
Laboratoire de Physiopathologie Métabolique et Rénale, Institut National de la Santé et de la Recherche Médicale, U499, Faculté de Médecine R.T.H. Laennec, rue G. Paradin, 69372 Lyon Cedex 08, France
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Bernard FERRIER
Bernard FERRIER
Laboratoire de Physiopathologie Métabolique et Rénale, Institut National de la Santé et de la Recherche Médicale, U499, Faculté de Médecine R.T.H. Laennec, rue G. Paradin, 69372 Lyon Cedex 08, France
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Publisher: Portland Press Ltd
Received:
June 22 2001
Revision Received:
August 24 2001
Accepted:
September 20 2001
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2001
2001
Biochem J (2001) 360 (2): 371–377.
Article history
Received:
June 22 2001
Revision Received:
August 24 2001
Accepted:
September 20 2001
Citation
Agnès CONJARD, Mireille MARTIN, Jérôme GUITTON, Gabriel BAVEREL, Bernard FERRIER; Gluconeogenesis from glutamine and lactate in the isolated humanrenal proximal tubule: longitudinal heterogeneity and lack of response to adrenaline. Biochem J 1 December 2001; 360 (2): 371–377. doi: https://doi.org/10.1042/bj3600371
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