DNA aptamer raised against receptor for advanced glycation end products suppresses renal tubular damage and improves insulin resistance in diabetic mice.

Abstract

OBJECTIVE:

Interaction of advanced glycation end products (AGEs) with the receptor RAGE plays a role in diabetic nephropathy. However, effects of RAGE-aptamer on tubular damage remain unknown. We examined whether RAGE-aptamer inhibited tubular damage in KKAy/Ta mice, obese type 2 diabetic mice with insulin resistance.

MATERIALS AND METHODS:

Male 8-week-old KKAy/Ta mice received continuous intraperitoneal infusion of either control-aptamer or RAGE-aptamer for 8 weeks. Blood biochemistry and blood pressure, and urinary N-acetyl-β-D-glucosaminidase (NAG) activity and albumin excretion levels were monitored. Kidney and adipose tissue samples were obtained for immunohistochemical analyses.

RESULTS:

Although RAGE-aptamer did not affect blood glucose, blood pressure, body weight, or serum creatinine values, it significantly inhibited the increase in urinary NAG activity and HOMA-IR in diabetic mice at 12 and 16 and at 16 weeks old, respectively. Furthermore, compared with control-aptamer-treated mice, renal carboxymethyllysine, RAGE, and NADPH oxidase-driven superoxide generation were significantly decreased in RAGE-aptamer-treated mice at 12 weeks old with subsequent amelioration of histological alterations in glomerular and interstitial area, while adipose tissue adiponectin expression was increased.

CONCLUSION:

Our present results suggest that RAGE-aptamer could inhibit tubular injury in obese type 2 diabetic mice partly by suppressing the AGE-RAGE-oxidative stress axis and improving insulin resistance.

• Authors: Ami Sotokawauchi, Takanori Matsui, Yuichiro Higashimoto, Yuri Nishino, Yoshinori Koga, Minoru Yagi, Sho-Ichi Yamagishi
• Journal: Diabetes & vascular disease research (Diab Vasc Dis Res) 2021 Jan-Feb Vol. 18 Issue 1 Pg. 1479164121990533 ISSN: 1752-8984 [Electronic] England
• PMID: 33535822 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ager protein, mouse
• Aptamers, Nucleotide
• Biomarkers
• Blood Glucose
• Glycation End Products, Advanced
• Insulin
• Receptor for Advanced Glycation End Products
• Acetylglucosaminidase

Topics

• Acetylglucosaminidase (urine)
• Animals
• Aptamers, Nucleotide (pharmacology)
• Biomarkers (blood, urine)
• Blood Glucose (metabolism)
• Diabetes Mellitus, Type 2 (blood, complications, drug therapy)
• Diabetic Nephropathies (etiology, metabolism, pathology, prevention & control)
• Disease Models, Animal
• Glycation End Products, Advanced (metabolism)
• Insulin (blood)
• Insulin Resistance
• Kidney Tubules (drug effects, metabolism, pathology)
• Male
• Mice
• Obesity (complications)
• Oxidative Stress (drug effects)
• Receptor for Advanced Glycation End Products (antagonists & inhibitors, metabolism)
• Signal Transduction