Glycation products and the pathogenesis of diabetic complications

Michael Brownlee

Research output: Contribution to journalArticle

348 Citations (Scopus)

Abstract

Glucose irreversibly modifies long-lived macromolecules by forming AGEs as a function of glucose concentration and time. AGEs cause qualitative and quantitative changes in extracellular matrix components such as type IV collagen, laminin, and vitronectin. These AGE-induced changes can affect cell adhesion, growth, and matrix accumulation. AGE-modified proteins also alter cell function by interacting with specific receptors on macrophages and endothelial cells, inducing changes that promote matrix overproduction, focal thrombosis, and vasoconstriction. DNA and nuclear proteins also may be targets for AGE damage. The persistence of accumulated AGEs during periods of normal glucose homeostasis may explain the phenomenon of hyperglycemic memory. Pharmacological inhibition of in vivo AGE formation by aminoguanidine prevents or ameliorates diabetic retinopathy, nephropathy, and neuropathy in animal models. These data suggest that aminoguanidine and other AGE inhibitors have a potential therapeutic role in the treatment of diabetic patients.

Original languageEnglish (US)
JournalDiabetes Care
Volume15
Issue number12
StatePublished - Dec 1992

Fingerprint

Diabetes Complications
Glucose
Cell-Matrix Junctions
Vitronectin
Collagen Type IV
Diabetic Neuropathies
Diabetic Nephropathies
Laminin
Diabetic Retinopathy
Nuclear Proteins
Vasoconstriction
Extracellular Matrix
Thrombosis
Homeostasis
Endothelial Cells
Animal Models
Macrophages
Pharmacology
DNA
Therapeutics

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Glycation products and the pathogenesis of diabetic complications. / Brownlee, Michael.

In: Diabetes Care, Vol. 15, No. 12, 12.1992.

Research output: Contribution to journalArticle

Brownlee, Michael. / Glycation products and the pathogenesis of diabetic complications. In: Diabetes Care. 1992 ; Vol. 15, No. 12.
@article{c34cb762490740a9b5dc7e6d5bc2ce6f,
title = "Glycation products and the pathogenesis of diabetic complications",
abstract = "Glucose irreversibly modifies long-lived macromolecules by forming AGEs as a function of glucose concentration and time. AGEs cause qualitative and quantitative changes in extracellular matrix components such as type IV collagen, laminin, and vitronectin. These AGE-induced changes can affect cell adhesion, growth, and matrix accumulation. AGE-modified proteins also alter cell function by interacting with specific receptors on macrophages and endothelial cells, inducing changes that promote matrix overproduction, focal thrombosis, and vasoconstriction. DNA and nuclear proteins also may be targets for AGE damage. The persistence of accumulated AGEs during periods of normal glucose homeostasis may explain the phenomenon of hyperglycemic memory. Pharmacological inhibition of in vivo AGE formation by aminoguanidine prevents or ameliorates diabetic retinopathy, nephropathy, and neuropathy in animal models. These data suggest that aminoguanidine and other AGE inhibitors have a potential therapeutic role in the treatment of diabetic patients.",
author = "Michael Brownlee",
year = "1992",
month = "12",
language = "English (US)",
volume = "15",
journal = "Diabetes Care",
issn = "1935-5548",
publisher = "American Diabetes Association Inc.",
number = "12",

}

TY - JOUR

T1 - Glycation products and the pathogenesis of diabetic complications

AU - Brownlee, Michael

PY - 1992/12

Y1 - 1992/12

N2 - Glucose irreversibly modifies long-lived macromolecules by forming AGEs as a function of glucose concentration and time. AGEs cause qualitative and quantitative changes in extracellular matrix components such as type IV collagen, laminin, and vitronectin. These AGE-induced changes can affect cell adhesion, growth, and matrix accumulation. AGE-modified proteins also alter cell function by interacting with specific receptors on macrophages and endothelial cells, inducing changes that promote matrix overproduction, focal thrombosis, and vasoconstriction. DNA and nuclear proteins also may be targets for AGE damage. The persistence of accumulated AGEs during periods of normal glucose homeostasis may explain the phenomenon of hyperglycemic memory. Pharmacological inhibition of in vivo AGE formation by aminoguanidine prevents or ameliorates diabetic retinopathy, nephropathy, and neuropathy in animal models. These data suggest that aminoguanidine and other AGE inhibitors have a potential therapeutic role in the treatment of diabetic patients.

AB - Glucose irreversibly modifies long-lived macromolecules by forming AGEs as a function of glucose concentration and time. AGEs cause qualitative and quantitative changes in extracellular matrix components such as type IV collagen, laminin, and vitronectin. These AGE-induced changes can affect cell adhesion, growth, and matrix accumulation. AGE-modified proteins also alter cell function by interacting with specific receptors on macrophages and endothelial cells, inducing changes that promote matrix overproduction, focal thrombosis, and vasoconstriction. DNA and nuclear proteins also may be targets for AGE damage. The persistence of accumulated AGEs during periods of normal glucose homeostasis may explain the phenomenon of hyperglycemic memory. Pharmacological inhibition of in vivo AGE formation by aminoguanidine prevents or ameliorates diabetic retinopathy, nephropathy, and neuropathy in animal models. These data suggest that aminoguanidine and other AGE inhibitors have a potential therapeutic role in the treatment of diabetic patients.

UR - http://www.scopus.com/inward/record.url?scp=11944272384&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=11944272384&partnerID=8YFLogxK

M3 - Article

VL - 15

JO - Diabetes Care

JF - Diabetes Care

SN - 1935-5548

IS - 12

ER -