The Activity of the Glucuronic Acid Pathway in Human and Experimental Diabetes

  • Albert I. Winegrad
  • Rex S. ClementsJr.
  • Paul J. Beisswenger
  • Constance L. Burden-Russell
Conference paper


The nature of the genetic defect in diabetes mellitus is unknown, and at present the data do not exclude its inheritance as a multifactorial trait. It is common knowledge that the experimental production of insulin deficiency in many mammalian species leads to gross abnormalities in glucose and lipid metabolism similar to those observed in patients with the juvenile form of diabetes. These patients characteristically have no detectable insulin on radio-immunoassay of their plasma, and require exogenous insulin for survival [1]. However, the relationship between gross insulin deficiency, or a more subtle abnormality in its normal regulatory role, and the development of the vascular complications of diabetes mellitus is obscure. Certainly no simple correlation has been established between the usual criteria of clinical “control” and the progression of disease of small or large blood vessels. Siperstein [2] has recently reported that if one biopsies the skeletal muscle of patients who have normal glucose tolerance but are presumed to be genetically constituted diabetics, because both of their parents are known to have the disease, one finds significant thickening of the capillary basement membrane in 50%. This observation has lead Siperstein [2] to suggest that thickening of the basement membrane reflects a primary inherited defect in the metabolism of small blood vessels which is followed only secondarily by the development of manifestations of insulin deficiency. This provocative conclusion rests upon two assumptions; first, that diabetes mellitus is inherited as an autosomal recessive; second, that a normal glucose tolerance excludes the presence of any derangement in metabolism resulting from an altered insulin regulatory mechanism.


Normal Glucose Tolerance Insulin Deficiency Human Diabetic Free Inositol Imidazole Acetic Acid 
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Copyright information

© Springer-Verlag, Berlin Heidelberg 1969

Authors and Affiliations

  • Albert I. Winegrad
    • 1
  • Rex S. ClementsJr.
    • 1
  • Paul J. Beisswenger
    • 1
  • Constance L. Burden-Russell
    • 1
  1. 1.George S. Cox Medical Research Institute Department of MedicineHospital of the University of PennsylvaniaPhiladelphiaUSA

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