Biochemical Derangements in Diabetes Mellitus

  • R. S. ClementsJr.
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 124)


During the fifty-sixth year since the discovery of insulin, most physicians who are concerned with the care of the diabetic have become more willing to accept the possibility that the development of diabetic complications may be related to the metabolic consequences of hyperglycemia. Since those tissues which require insulin for the intracellular transport of glucose (i.e., muscle and fat) appear to be relatively immune to the ravages of diabetes, current research into the mechanisms by which an elevated glucose concentration could result in cellular damage has focused upon the so-called “noninsulin-dependent pathways of glucose metabolism.” Obviously, this term implies that, whereas these pathways are not directly activated by insulin, the hyperglycemia which results from insulin deficiency does foster their activation. It is the purpose of this review to consider certain of these pathways and the roles which they have been speculated to play in the development of diabetic complications.


Diabetic Neuropathy Diabetic Animal Glomerular Basement Membrane Aldose Reductase Nerve Conduction Velocity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Beisswenger, P.J. 1976. Glomerular basement membrane: Biosynthesis and chemical composition in the streptozotocin diabetic rat. J. Clin. Invest. 58:844–852.PubMedCrossRefGoogle Scholar
  2. Beisswenger, P.J. and Spiro, R.G. 1970. Human glomerular basement membrane: Chemical alteration in diabetes mellitus. Science 168:596–598.PubMedCrossRefGoogle Scholar
  3. Bunn, H.F., Haney, D.N., Gabbay, K.H., and Gallop, P.M. 1975. Further identification of the nature and linkage of the carbohydrate in hemoglobin AIc Bio ehem. Biophys. Res. Commun. 67:103–109.CrossRefGoogle Scholar
  4. Caspary, W.F. and Crane, R.K. 1970. Active transport of myoinositol and its relation to the sugar transport system in hamster small intestine. Biochim. Biophys. Acta 203:308–316.PubMedCrossRefGoogle Scholar
  5. Chylack, L.T. Jr. and Kinoshita, J.H. 1969. A biochemical evaluation of a cataract induced in a high glucose medium. Invest. Ophthal. 8:401–412.PubMedGoogle Scholar
  6. Clements, R.S. Jr., Morrison, A.D., and Winegrad, A.I. 1969. Polyol pathway in aorta: Regulation by hormones. Science 166:1007–1008.PubMedCrossRefGoogle Scholar
  7. Clements, R.S. Jr. and Reynertson, R. 1977. Myoinositol metabolism in diabetes mellitus: Effect of insulin treatment. Diabetes 26:215–221.PubMedCrossRefGoogle Scholar
  8. Clements, R.S. Jr. and Rhoten, W.B. 1976. Phosphoinositide metabolism and insulin secretion from isolated rat pancreatic islets. J. Clin. Invest. 57:684–691.PubMedCrossRefGoogle Scholar
  9. Clements, R.S. Jr., Weaver, J.P., and Winegrad, A.I. 1969. The distribution of polyol:NADP oxidoreductase in mammalian tissues. Biochem. Biophys. Res. Commun. 37:347–353.PubMedCrossRefGoogle Scholar
  10. Cohen, M.P. and Vogt, C. 1972. Evidence for enchanced basement membrane synthesis and lysine hydroxylation in renal glomerulus in experimental diabetes. Biochem. Biophys. Res. Commun. 49:1542–1546.PubMedCrossRefGoogle Scholar
  11. Colwell, J.A., Chambers, A., and Laimins, M. 1975. Inhibition of labile aggregation-stimulating substance (LASS) and platelet aggregation in diabetes mellitus. Diabetes 24:684–687.PubMedCrossRefGoogle Scholar
  12. Fushimi, H. and Tarui, S. 1976. β-glycosidases and diabetic microangiopathy. I. Decreases of β-glycosidase activities in diabetic rat kidney. J. Biochem. 79:265–270.PubMedGoogle Scholar
  13. Gabbay, K.H. 1973. pp 417–424. IN R.A. Camerini-Davalos and H.S. Cole (Eds.) Vascular and neurologic changes in early diabetes. New York: Academic Press.Google Scholar
  14. Gabbay, K.H., Merola, L.O., and Field, R.A. 1966. Sorbitol pathway: Presence in nerve and cord with substrate accumulation in diabetes. Science 151:209–210.PubMedCrossRefGoogle Scholar
  15. Gandhi, V.S. and Bleicher, S.J. 1975. “Fast” hemoglobin, diabetes and pregnancy. Diabetes 24:415.Google Scholar
  16. Grant, M.E., Kefalides, N.A., and Prockop, D.J. 1972. The biosynthesis of basement membrane collagen in embryonic chick cells and a time-dependent conversion to chains in intact lens. J. Biol. Chem. 247:3545–3551.PubMedGoogle Scholar
  17. Greene, D.A., De Jesus, P.V., and Winegrad, A.I. 1975. Effects of insulin and dietary myoinositol on impaired peripheral motor nerve conduction velocity in acute streptozotocin diabetes. J. Clin. Invest. 55:1326–1336.PubMedCrossRefGoogle Scholar
  18. Hendrickson, H.S. and Reinertsen, J.L. 1971. Phosphoinositide interconversion: A model for control of Na+ and K permeability in the nerve axon membrane. Biochem. Biophys. Res. Commun. 44:1258–1264.PubMedCrossRefGoogle Scholar
  19. Kefalides, N.A. 1974. Biochemical properties of human glomerular basement membrane in normal and diabetic kidneys. J. Clin. Invest. 53:403–407.PubMedCrossRefGoogle Scholar
  20. Khalifa, A.S. and Cohen, M.P. 1975. Glomerular protocollagen lysylhydroxylase activity in streptozotocin diabetes. Biochim. Biophys. Acta 386:332–339.PubMedCrossRefGoogle Scholar
  21. Kinoshita, J.H. 1965. Cataracts in galactosemia. Invest. Ophthal. 4:786–799.PubMedGoogle Scholar
  22. Kuck, J.F.R. Jr. 1970. Response of the mouse lens to high concentrations of glucose or galactose. Ophthal. Res. 1:166–174.CrossRefGoogle Scholar
  23. Lemback, K. and Charalampous, F.C. 1967. Metabolic functions of myoinositol. VI. Impairment of amino acid transport in KB cells caused by inositol deficiency. J. Biol. Chem. 242: 2606–2614.Google Scholar
  24. McMillan, D.E. 1972. Elevation of glycoprotein fucose in diabetes mellitus. Diabetes 21:863–871.PubMedGoogle Scholar
  25. Micheli, R.H. 1975. Inositol phospholipids and cell surface receptor function. Biochim. Biophys. Acta 415:81–147.CrossRefGoogle Scholar
  26. Morrison, A.D., Clements, R.S. Jr., and Winegrad, A.I. 1973. Effects of elevated glucose concentrations on the metabolism of the aortic wall. J. Clin. Invest. 51:3114–3123.CrossRefGoogle Scholar
  27. Peterson, C.M., Jones, R.L., Koenig, R.J., Melvin, E.T., and Lehrman, M.L. 1977. Reversible hematologic sequelae of diabetes mellitus. Ann. Int. Med. 86:425–429.PubMedGoogle Scholar
  28. Pumphrey, A.M. 1969. Incorporation of (32P) orthophosphate into brain-slice phospholipids and their precursors: Effects of electrical stimulation. Biochem. J. 112:61–70.PubMedGoogle Scholar
  29. Stewart, M.A., Kurien, M.M., Sherman, W.R., and Cotlier, E.V. 1968. Inositol changes in nerve and lens of galactose fed rats. J. Neuroohem. 15:941–946.CrossRefGoogle Scholar
  30. Stewart, M.A., Sherman, W.R., Kurien, M.M., Moonsammy, G.I., and Wisgerhof, M. 1967. Polyol accumulations in nervous tissue of rats with experimental diabetes and galactosemia. J. Neuroohem. 14:1057–1066.CrossRefGoogle Scholar
  31. Stevens, V.J., Vlassara, H., Abati, A., and Cerami, A. 1977. Nonenzymatic glycosylation of hemoglobin. J. Biol. Chem. 252: 2998–3002.PubMedGoogle Scholar
  32. Takenawa, T. and Egawa, K. 1977. CDP-diglyceride:.inositol transferase from rat liver. J. Biol. Chem. 252:5419–5423.PubMedGoogle Scholar
  33. van Heyningen, R. 1959. Formation of polyols by the lens of the rat with “sugar” cataract. Nature 184:194–195.CrossRefGoogle Scholar
  34. Wahl, P., Deppermann, D., Deschner, W., Fuchs, E., and Rexroth, W. 1973. pp. 147–153. IN R.A. Camerini-Davolos and H.S. Cole (Eds.) Vascular and neurologic changes in early diabetes. New York: Academic Press.Google Scholar
  35. Waitzman, M.B., Colley, A.M., and Nardelli-Olkoska, K. 1977. Metabolic approaches to studies on diabetic microangiopathy. Diabetes 26:510–517.PubMedCrossRefGoogle Scholar
  36. Westberg, N.G. and Michael, A.F. 1973. Human glomerular basement membrane: Chemical composition in diabetes mellitus. Acta Med. Scand. 144:39–47.Google Scholar

Discussion References

  1. Cerami, A., Koenig, R.J., Peterson, C.M., and Stevens, V.M. 1978. Formation of Hb AIc as a biochemical model for the sequelae of diabetes. IN George Brewer (Ed.) Proc. 4 th Internat’l. Conf. on Red Cell Metabol. and Funct., Ann Arbor, MI. New York: Alan R. Liss, Inc. In press.Google Scholar
  2. Cole, R.A., Bunn, H.F., and Soeldner, J.S. 1977. New rapid assay method for hemoglobin Hb AIc and total fast (abstract). Diabetes 26(Suppl. 1):392.Google Scholar
  3. Fluckiger, R. and Winterhalter, K.H. 1976. In-vitro synthesis of hemoglobin AIc. FEBS Lett. 71:356–360.PubMedCrossRefGoogle Scholar
  4. Javid, J. Pettis, P.K., Koenig, R.J., and Cerami, A. 1978. Immunologic characterization and quantification of Hb AIc. Brit. J. Haematol. 38:329–337.CrossRefGoogle Scholar
  5. Koenig, R.J., Peterson, C.M., Jones, R.L., Saudek, C., Lehrman, M., and Cerami, A. 1976. The correlation of glucose regulation and hemoglobin AIc in diabetes mellitus. New Eng. J. Med. 295:417–420.PubMedCrossRefGoogle Scholar
  6. Schmidt, G.E., Martin, A.P., Townsend, J.R., and Vorbeck, M.L. 1977. Basement membrane synthesis in spontaneously diabetic Mystromys albicaudatus. J. Cell Biol. 75:155a. (Abstr.)Google Scholar
  7. Stevens, V.S., Vlassara, H., Abati, A., and Cerami, A. 1977. Nonenzymatic glycosylation of hemoglobin. J. Biol. Chem. 252: 2998–3002.PubMedGoogle Scholar
  8. Trivelli, L.A., Ranney, H.M., and Lai, H-T. 1971. Hemoglobin components in patients with diabetes mellitus. New Eng. J. Med. 284:353–357.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1979

Authors and Affiliations

  • R. S. ClementsJr.
    • 1
  1. 1.Diabetes Research and Training CenterUniversity of Alabama School of MedicineBirminghamUSA

Personalised recommendations