Prolonged hyperglycemia is the primary metabolic abnormality responsible for the development of irreversible tissue damage in chronic diabetes. However, patients with similar levels of chronic hyperglycemia can differ markedly in their susceptibility to diabetic complications. Among the mechanisms by which hyperglycemia may lead to tissue damage, nonenzymatic glycosylation involves excessive chemical attachment of glucose to proteins without the involvement of enzymes. The early Amadori products, resembling hemoglobin A1c, slowly give rise to complex irreversible glycosylation adducts. Only these post-Amadori products accumulate in diabetic tissues over long periods. However, early nonenzymatic glycosylation or Amadori product formation can alter such physiological processes as enzyme activity or binding of regulatory molecules. Advanced glycosylation end products can covalently trap extravasated serum proteins to the extravascular matrix, and thus may contribute to capillary closure in the retina and glomerulus, and to arterial narrowing in the coronary, cerebral, and peripheral circulation. Although a macrophage receptor system may antagonize this glycosylation-mediated accumulation of proteins by recognizing and ingesting those proteins with advanced glycosylation end products, excessive formation of those proteins in diabetes may saturate the capacity of the macrophage removal system.
|Original language||English (US)|
|Issue number||10 Suppl|
|Publication status||Published - Oct 1 1986|
ASJC Scopus subject areas
- Clinical Biochemistry
- Biochemistry, medical