Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1982 May;69(5):1164–1168. doi: 10.1172/JCI110552

Regulation of hemoglobin AIc formation in human erythrocytes in vitro. Effects of physiologic factors other than glucose.

R J Smith, R J Koenig, A Binnerts, J S Soeldner, T T Aoki
PMCID: PMC370181  PMID: 7068852

Abstract

The formation of hemoglobin AIc was studied in intact human erythrocytes in vitro. Satisfactory methods were developed for maintaining erythrocytes under physiologic conditions for greater than 8 d with less than 10% hemolysis. Hemoglobin AIc levels were determined chromatographically on erythrocyte hemolysates after removal of reversible components by incubation for 6 h at 37 degree C. Hemoglobin AIc concentration was found to increase linearly with time during 8 d of incubation. The rate of formation of hemoglobin AIc increased linearly as glucose concentration was increased from 40 to 1,000 mg/dl. Deoxyhemoglobin was glycosylated twice as rapidly as oxyhemoglobin. The rate of hemoglobin AIc formation was further increased by elevated 2,3-diphosphoglycerate levels, an effect that was most marked with deoxyhemoglobin. We conclude that the nonenzymatic glycosylation of hemoglobin is influenced by factors other than glucose, including oxygen tension and 2,3-diphosphoglycerate levels.

Full text

PDF
1164

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bunn H. F., Haney D. N., Gabbay K. H., Gallop P. M. Further identification of the nature and linkage of the carbohydrate in hemoglobin A1c. Biochem Biophys Res Commun. 1975 Nov 3;67(1):103–109. doi: 10.1016/0006-291x(75)90289-2. [DOI] [PubMed] [Google Scholar]
  2. Bunn H. F., Haney D. N., Kamin S., Gabbay K. H., Gallop P. M. The biosynthesis of human hemoglobin A1c. Slow glycosylation of hemoglobin in vivo. J Clin Invest. 1976 Jun;57(6):1652–1659. doi: 10.1172/JCI108436. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cole R. A., Soeldner J. S., Dunn P. J., Bunn H. F. A rapid method for the determination of glycosylated hemoglobins using high pressure liquid chromatography. Metabolism. 1978 Mar;27(3):289–301. doi: 10.1016/0026-0495(78)90109-9. [DOI] [PubMed] [Google Scholar]
  4. Ditzel J., Standl E. The oxygen transport system of red blood cells during diabetic ketoacidosis and recovery. Diabetologia. 1975 Aug;11(4):255–260. doi: 10.1007/BF00422388. [DOI] [PubMed] [Google Scholar]
  5. Flückiger R., Winterhalter K. H. In vitro synthesis of hemoglobin AIc. FEBS Lett. 1976 Dec 1;71(2):356–360. doi: 10.1016/0014-5793(76)80969-6. [DOI] [PubMed] [Google Scholar]
  6. Koenig R. J., Blobstein S. H., Cerami A. Structure of carbohydrate of hemoglobin AIc. J Biol Chem. 1977 May 10;252(9):2992–2997. [PubMed] [Google Scholar]
  7. Koenig R. J., Cerami A. Synthesis of hemoglobin AIc in normal and diabetic mice: potential model of basement membrane thickening. Proc Natl Acad Sci U S A. 1975 Sep;72(9):3687–3691. doi: 10.1073/pnas.72.9.3687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Koenig R. J., Peterson C. M., Jones R. L., Saudek C., Lehrman M., Cerami A. Correlation of glucose regulation and hemoglobin AIc in diabetes mellitus. N Engl J Med. 1976 Aug 19;295(8):417–420. doi: 10.1056/NEJM197608192950804. [DOI] [PubMed] [Google Scholar]
  9. Lee C. K., Manning J. M. Kinetics of the carbamylation of the amino groups of sickle cell hemoglobin by cyanate. J Biol Chem. 1973 Aug 25;248(16):5861–5865. [PubMed] [Google Scholar]
  10. Matthew J. B., Morrow J. S., Wittebort R. J., Gurd F. R. Quantitative determination of carbamino adducts of alpha and beta chains in human adult hemoglobin in presence and absence of carbon monoxide and 2,3-diphosphoglycerate. J Biol Chem. 1977 Apr 10;252(7):2234–2244. [PubMed] [Google Scholar]
  11. Oski F. A., Gottlieb A. J., Delivoria-Papadopoulos M., Miller W. W. Red-cell 2,3-diphosphoglycerate levels in subjects with chronic hypoxemia. N Engl J Med. 1969 May 22;280(21):1165–1166. doi: 10.1056/NEJM196905222802108. [DOI] [PubMed] [Google Scholar]
  12. Oski F. A., Travis S. F., Miller L. D., Delivoria-Papadopoulos M., Cannon E. The in vitro restoration of red cell 2,3-diphosphoglycerate levels in banked blood. Blood. 1971 Jan;37(1):52–58. [PubMed] [Google Scholar]
  13. Spicer K. M., Allen R. C., Hallett D., Buse M. G. Synthesis of hemoglobin Aic and related minor hemoglobin by erythrocytes. In vitro study of regulation. J Clin Invest. 1979 Jul;64(1):40–48. doi: 10.1172/JCI109461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Stevens V. J., Vlassara H., Abati A., Cerami A. Nonenzymatic glycosylation of hemoglobin. J Biol Chem. 1977 May 10;252(9):2998–3002. [PubMed] [Google Scholar]
  15. Trivelli L. A., Ranney H. M., Lai H. T. Hemoglobin components in patients with diabetes mellitus. N Engl J Med. 1971 Feb 18;284(7):353–357. doi: 10.1056/NEJM197102182840703. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES