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Research Article Free access | 10.1172/JCI105610

Acid-Base Alterations and Renal Gluconeogenesis: Effect of pH, Bicarbonate Concentration, and PCO2

Donald E. Kamm, Robert E. Fuisz, A. David Goodman, and George F. Cahill Jr.

Elliott P. Joslin Research Laboratory in the Department of Medicine, Harvard Medical School, the Peter Bent Brigham Hospital, and the Diabetes Foundation, Inc., Boston, Mass

†

This work done during tenure as a research fellow of the National Institutes of Health. Present address: University of Rochester School of Medicine and Dentistry and the Rochester General Hospital, Rochester, N. Y.

‡

Special fellow, National Institutes of Health.

§

This work done during tenure as a clinical trainee in endocrinology, National Institutes of Health. Present address: Albany Medical College, Albany, N. Y.

ǁ

Investigator, Howard Hughes Medical Institute.

Address requests for reprints to Dr. George F. Cahill, Jr., 170 Pilgrim Rd., Boston, Mass. 02215.

*

Submitted for publication November 1, 1966; accepted March 21, 1967.

Presented in part at the Annual Meeting of the American Society for Clinical Investigation, May 1965 (1), and before the Eastern Section of the American Federation for Clinical Research, December 1965 (2).

Supported in part by U. S. Public Health Service grants TI AM 5077-09, AM 09584-01, and AM 09232-01 and by the John A. Hartford Foundation.

Find articles by Kamm, D. in: JCI | PubMed | Google Scholar

Elliott P. Joslin Research Laboratory in the Department of Medicine, Harvard Medical School, the Peter Bent Brigham Hospital, and the Diabetes Foundation, Inc., Boston, Mass

†

This work done during tenure as a research fellow of the National Institutes of Health. Present address: University of Rochester School of Medicine and Dentistry and the Rochester General Hospital, Rochester, N. Y.

‡

Special fellow, National Institutes of Health.

§

This work done during tenure as a clinical trainee in endocrinology, National Institutes of Health. Present address: Albany Medical College, Albany, N. Y.

ǁ

Investigator, Howard Hughes Medical Institute.

Address requests for reprints to Dr. George F. Cahill, Jr., 170 Pilgrim Rd., Boston, Mass. 02215.

*

Submitted for publication November 1, 1966; accepted March 21, 1967.

Presented in part at the Annual Meeting of the American Society for Clinical Investigation, May 1965 (1), and before the Eastern Section of the American Federation for Clinical Research, December 1965 (2).

Supported in part by U. S. Public Health Service grants TI AM 5077-09, AM 09584-01, and AM 09232-01 and by the John A. Hartford Foundation.

Find articles by Fuisz, R. in: JCI | PubMed | Google Scholar

Elliott P. Joslin Research Laboratory in the Department of Medicine, Harvard Medical School, the Peter Bent Brigham Hospital, and the Diabetes Foundation, Inc., Boston, Mass

†

This work done during tenure as a research fellow of the National Institutes of Health. Present address: University of Rochester School of Medicine and Dentistry and the Rochester General Hospital, Rochester, N. Y.

‡

Special fellow, National Institutes of Health.

§

This work done during tenure as a clinical trainee in endocrinology, National Institutes of Health. Present address: Albany Medical College, Albany, N. Y.

ǁ

Investigator, Howard Hughes Medical Institute.

Address requests for reprints to Dr. George F. Cahill, Jr., 170 Pilgrim Rd., Boston, Mass. 02215.

*

Submitted for publication November 1, 1966; accepted March 21, 1967.

Presented in part at the Annual Meeting of the American Society for Clinical Investigation, May 1965 (1), and before the Eastern Section of the American Federation for Clinical Research, December 1965 (2).

Supported in part by U. S. Public Health Service grants TI AM 5077-09, AM 09584-01, and AM 09232-01 and by the John A. Hartford Foundation.

Find articles by Goodman, A. in: JCI | PubMed | Google Scholar

Elliott P. Joslin Research Laboratory in the Department of Medicine, Harvard Medical School, the Peter Bent Brigham Hospital, and the Diabetes Foundation, Inc., Boston, Mass

†

This work done during tenure as a research fellow of the National Institutes of Health. Present address: University of Rochester School of Medicine and Dentistry and the Rochester General Hospital, Rochester, N. Y.

‡

Special fellow, National Institutes of Health.

§

This work done during tenure as a clinical trainee in endocrinology, National Institutes of Health. Present address: Albany Medical College, Albany, N. Y.

ǁ

Investigator, Howard Hughes Medical Institute.

Address requests for reprints to Dr. George F. Cahill, Jr., 170 Pilgrim Rd., Boston, Mass. 02215.

*

Submitted for publication November 1, 1966; accepted March 21, 1967.

Presented in part at the Annual Meeting of the American Society for Clinical Investigation, May 1965 (1), and before the Eastern Section of the American Federation for Clinical Research, December 1965 (2).

Supported in part by U. S. Public Health Service grants TI AM 5077-09, AM 09584-01, and AM 09232-01 and by the John A. Hartford Foundation.

Find articles by Cahill, G. in: JCI | PubMed | Google Scholar

Published July 1, 1967 - More info

Published in Volume 46, Issue 7 on July 1, 1967
J Clin Invest. 1967;46(7):1172–1177. https://doi.org/10.1172/JCI105610.
© 1967 The American Society for Clinical Investigation
Published July 1, 1967 - Version history
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Abstract

In previous studies it was found that renal cortical slices from rats with induced metabolic acidosis have an increased capacity to produce glucose, whereas cortical slices from rats with metabolic alkalosis manifest decreased gluconeogenesis. To evaluate the relative influence of extracellular fluid pH, [HCO3-], and carbon dioxide tension on renal gluconeogenesis, we observed glucose production by cortex from rats with induced respiratory acidosis, and by cortex taken from normal animals and incubated in acid and alkaline media.

We found glucose production to be increased in cortex from rats with respiratory acidosis, as is the case in metabolic acidosis. Glucose production by slices from normal rats was increased in media made acidic by reducing [HCO3-], and decreased in media made alkaline by raising [HCO3-]. These effects were evident whether the gluconeogenic substrate employed was glutamine, glutamate, α-ketoglutarate, or oxalacetate. Glucose production was also increased in media made acidic by raising CO2 tension and decreased in media made alkaline by reducing CO2 tension. These data indicate that both in vivo and in vitro, pH, rather than CO2 tension or [HCO3-], is the most important acid-base variable affecting renal gluconeogenesis.

The findings suggest that a decrease in extracellular fluid pH enhances renal gluconeogenesis through direct stimulation of one of the rate-limiting reactions involved in the conversion of oxalacetate to glucose. We hypothesize that the resultant increase in the rate of removal of glutamate, a precursor of oxalacetate, may constitute an important step in the mechanism by which acidosis increases renal ammonia production.

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