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Original Articles

Glutamine and Alanine Metabolism in NIDDM

  1. Michael Stumvoll,
  2. Gabriele Perriello,
  3. Nurjahan Nurjhan,
  4. Stephen Welle,
  5. John Gerich,
  6. Arthur Bucci,
  7. Per-Anders Jansson,
  8. George Dailey,
  9. Dennis Bier,
  10. Trond Jenssen and
  11. John Gerich
  1. University of Rochester School of Medicine Rochester, New York
  2. Department of Medicine, University of Pittsburgh Pittsburgh, Pennsylvania
  3. Division of Endocrinology and Metabolism Scripps Clinic La Jolla, California
  4. Metabolism Division, Washington University School of Medicine St. Louis, Missouri
  5. Department of Medicine, University Hospital of Tromsø Tromsø, Norway
  1. Address correspondence and reprint requests to Dr. John E. Gerich, University of Rochester, 601 Elmwood Ave., Box MED/CRC, Rochester, NY 14642.
Diabetes 1996 Jul; 45(7): 863-868. https://doi.org/10.2337/diab.45.7.863
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Abstract

Gluconeogenesis is increased in NIDDM. We therefore examined the metabolism of glutamine and alanine, the most important gluconeogenic amino acids, in 14 postabsorptive NIDDM subjects and 18 nondiabetic volunteers using a combination of isotopic ([6-3H] glucose (20 µCi, 0.2 µCi/min), [U-14C]glutamine (20 µCi, 0.2 µCi/min), [3-13C]alanine (99% 13C, 2 mmol, 20 µmol/min), [ring-2H5]phenylalanine (99% 2H, 2 µmol/kg, 0.03 µmol · kg-1 · min-1), and limb balance techniques. Alanine turnover (4.54 ± 0.24 vs. 5.64 ± 0.33 µmol · kg-1 · min-1), de novo, synthesis (3.00 ± 0.25 vs. 4.01 ± 0.33 µmol · kg-1 · min-1) were increased in NIDDM subjects (all P < 0.001), while its forearm release (0.45 ± 0.04 vs. 0.39 ± 0.04 µmol · kg-1 · min-1) was unaltered. Although glutamine turnover (4.81 ± 0.23 vs. 4.40 ± 0.31 µmol · kg-1 · min-1) was unaltered in NIDDM, its conversion to glucose (0.57 ± 0.04 vs. 1.08 ± 0.10 µmol · kg-1 · min-1) and to alanine (0.10 ± 0.01 vs. 0.34 ± 0.04 µmol · kg-1 · min-1) (both P = 0.001) was increased while its oxidation (2.84 ± 0.27 vs. 1.84 ± 0.15 µmol kg-1 · min-1 P = 0.03) and forearm release (0.77 ± 0.05 vs. 0.62 ± 0.09 µmol · kg-1 · min-1 P < 0.008) were both reduced. Our results thus demonstrate that there are substantial alterations of glutamine and alanine metabolism in NIDDM. Conversion of both amino acids to glucose and the proportion of their turnover used for gluconeogenesis are increased; release of both amino acids from tissues other than skeletal muscle seems to be increased. Finally, the reduction in glutamine oxidation, possibly the result of competition with glucose and free fatty acids as fuels, makes more glutamine available for gluconeogenesis without a change in its turnover.

  • Received August 3, 1995.
  • Revision received February 5, 1996.
  • Accepted February 5, 1996.
  • Copyright © 1996 by the American Diabetes Association

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July 1996, 45(7)
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Glutamine and Alanine Metabolism in NIDDM
Michael Stumvoll, Gabriele Perriello, Nurjahan Nurjhan, Stephen Welle, John Gerich, Arthur Bucci, Per-Anders Jansson, George Dailey, Dennis Bier, Trond Jenssen, John Gerich
Diabetes Jul 1996, 45 (7) 863-868; DOI: 10.2337/diab.45.7.863

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Glutamine and Alanine Metabolism in NIDDM
Michael Stumvoll, Gabriele Perriello, Nurjahan Nurjhan, Stephen Welle, John Gerich, Arthur Bucci, Per-Anders Jansson, George Dailey, Dennis Bier, Trond Jenssen, John Gerich
Diabetes Jul 1996, 45 (7) 863-868; DOI: 10.2337/diab.45.7.863
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