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AGE down-regulation of monocyte RAGE expression and its association with diabetic complications in type 1 diabetes

Junnosuke Miura1, Yasuko Uchigata, Yasuhiko Yamamoto

  • 1Diabetes Center, Tokyo Women's Medical University School of Medicine, 8-1, Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. jmiurara@dmc.twmu.ac.jp

Journal of Diabetes and Its Complications
|March 17, 2004
PubMed

Insights

Advanced glycation end product (AGE) receptor (RAGE) mRNA levels are lower in type 1 diabetic patients with vascular complications. AGE exposure down-regulates RAGE, suggesting a role in diabetic complications.

Area of Science:

  • Biochemistry
  • Immunology
  • Endocrinology

Background:

  • Advanced glycation end products (AGEs) and their receptor (RAGE) are implicated in diabetic complications.
  • RAGE plays a crucial role in cellular responses to AGEs.

Purpose of the Study:

  • To investigate RAGE mRNA levels in monocytes of type 1 diabetic patients.
  • To analyze the relationship between RAGE expression and diabetic vascular complications.

Main Methods:

  • Quantitative reverse transcription-polymerase chain reaction (RT-PCR) to measure RAGE mRNA.
  • Monocyte-enriched cultures exposed to glyceraldehyde-derived AGEs.
  • Assay of serum AGEs and carboxymethyllysine (CML) levels.

Main Results:

  • Monocyte RAGE mRNA was significantly lower in diabetic patients with retinopathy and nephropathy.
  • Glyceraldehyde-derived AGE exposure down-regulated RAGE mRNA and protein in monocytes.
  • A negative correlation was observed between serum AGE/CML levels and monocyte RAGE mRNA.

Conclusions:

  • Decreased monocyte RAGE expression in type 1 diabetes may be due to AGE ligand engagement.
  • Reduced RAGE expression could contribute to the pathogenesis of diabetic vascular complications.

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