Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1972 Dec;51(12):3114–3123. doi: 10.1172/JCI107138

Effects of Elevated Glucose Concentrations on the Metabolism of the Aortic Wall

Anthony D Morrison 1,2, Rex S Clements Jr 1,2, Albert I Winegrad 1,2
PMCID: PMC332993  PMID: 4640951

Abstract

The effects of elevated glucose concentrations on the metabolism of the aortic wall were examined in a preparation of tubular segments of rabbit descending thoracic aorta comprised of intima and media only. Increased medium glucose concentrations (20-50 mm) resulted in increased aortic sorbitol and fructose concentrations and an increased rate of fructose release into the medium. This increased flux through the polyol pathway can be explained as a consequence both of an increased free intracellular glucose concentration and of the kinetic characteristics of the alditol: NADP oxidoreductase and the l-iditol: NAD oxidoreductase isolated and partially purified from rabbit thoracic aorta. Incubation with elevated glucose concentrations for 2 or more hr was also associated with a significant increase in the water content of the tissue without a significant increase in the inulin space. The oxygen uptake of the tissues incubated with elevated glucose concentrations was significantly reduced; this appears to result from a limitation imposed by oxygen diffusion at physiological oxygen tensions. A compensatory increase in glycolysis and an increase in the aortic lactate/pyruvate concentration ratio were also observed. The oxygen uptake and lactate production of tissue incubated with 50 mm glucose could be preserved at rates observed in tissue incubated with a physiological glucose concentration by the addition of 40 mm mannitol to the medium. Aortic intima and media from alloxan-diabetic rabbits also exhibit an increased water content and a decreased rate of oxygen uptake. These observations suggest that elevated ambient glucose concentrations result in significant alterations in the metabolism of aortic intima and media.

Full text

PDF
3114

Selected References

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

  1. Britton H. G., Huggett A. S., Nixon D. A. Carbohydrate metabolism in the sheep placenta. Biochim Biophys Acta. 1967 Apr 25;136(3):426–440. doi: 10.1016/0304-4165(67)90002-5. [DOI] [PubMed] [Google Scholar]
  2. Chylack L. T., Jr, Kinoshita J. H. A biochemical evaluation of a cataract induced in a high-glucose medium. Invest Ophthalmol. 1969 Aug;8(4):401–412. [PubMed] [Google Scholar]
  3. Clements R. S., Jr, Morrison A. D., Winegrad A. I. Polyol pathway in aorta: regulation by hormones. Science. 1969 Nov 21;166(3908):1007–1008. doi: 10.1126/science.166.3908.1007. [DOI] [PubMed] [Google Scholar]
  4. Clements R. S., Jr, Winegrad A. I. Modulation of mammalian polyol: NADP oxidoreductase activity by ADP and ATP. Biochem Biophys Res Commun. 1969 Sep 10;36(6):1006–1012. doi: 10.1016/0006-291x(69)90304-0. [DOI] [PubMed] [Google Scholar]
  5. Clements R. S., Jr, Winegrad A. I. Purification of alditol: NADP oxidoreductase from human placenta. Biochem Biophys Res Commun. 1972 Jun 28;47(6):1473–1479. doi: 10.1016/0006-291x(72)90238-0. [DOI] [PubMed] [Google Scholar]
  6. HAYMAN S., KINOSHITA J. H. ISOLATION AND PROPERTIES OF LENS ALDOSE REDUCTASE. J Biol Chem. 1965 Feb;240:877–882. [PubMed] [Google Scholar]
  7. HERS H. G. [The mechanism of the formation of seminal fructose and fetal fructose]. Biochim Biophys Acta. 1960 Jan 1;37:127–138. doi: 10.1016/0006-3002(60)90086-x. [DOI] [PubMed] [Google Scholar]
  8. KLINGENBERG M., BUECHER T. Biological oxidations. Annu Rev Biochem. 1960;29:669–708. doi: 10.1146/annurev.bi.29.070160.003321. [DOI] [PubMed] [Google Scholar]
  9. LOWRY O. H., PASSONNEAU J. V., HASSELBERGER F. X., SCHULZ D. W. EFFECT OF ISCHEMIA ON KNOWN SUBSTRATES AND COFACTORS OF THE GLYCOLYTIC PATHWAY IN BRAIN. J Biol Chem. 1964 Jan;239:18–30. [PubMed] [Google Scholar]
  10. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  11. SMITH M. G. Polyol dehydrogenases. 4. Crystallization of the L-iditol dehydrogenase of sheep liver. Biochem J. 1962 Apr;83:135–144. doi: 10.1042/bj0830135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. TOBIAN L. The electrolytes of arterial wall in experimental renal hypertension. Circ Res. 1956 Nov;4(6):671–675. doi: 10.1161/01.res.4.6.671. [DOI] [PubMed] [Google Scholar]
  13. Tobian L., Olson R., Chesley G. Water content of arteriolar wall in renovascular hypertension. Am J Physiol. 1969 Jan;216(1):22–24. doi: 10.1152/ajplegacy.1969.216.1.22. [DOI] [PubMed] [Google Scholar]
  14. Travis S. F., Morrison A. D., Clements R. S., Jr, Winegrad A. I., Oski F. A. Metabolic alterations in the human erythrocyte produced by increases in glucose concentration. The role of the polyol pathway. J Clin Invest. 1971 Oct;50(10):2104–2112. doi: 10.1172/JCI106704. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. VAN HAYNINGEN R. The sorbital pathway in the lens. Exp Eye Res. 1962 Jun;1:396–404. doi: 10.1016/s0014-4835(62)80029-3. [DOI] [PubMed] [Google Scholar]
  16. Whereat A. F. Recent advances in experimental and molecular pathology. Atherosclerosis and metabolic disorder in the arterial wall. Exp Mol Pathol. 1967 Oct;7(2):233–247. doi: 10.1016/0014-4800(67)90032-9. [DOI] [PubMed] [Google Scholar]
  17. YALCIN S., WINEGRAD A. I. DEFECT IN GLUCOSE METABOLISM IN AORTIC TISSUE FROM ALLOXAN DIABETIC RABBITS. Am J Physiol. 1963 Dec;205:1253–1259. doi: 10.1152/ajplegacy.1963.205.6.1253. [DOI] [PubMed] [Google Scholar]

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

RESOURCES