DNA Aptamer Raised Against Receptor for Advanced Glycation End Products Suppresses Renal Tubular Damage and Improves Insulin Resistance in Diabetic Mice

Overview

Journal Diab Vasc Dis Res

Publisher Sage Publications

Specialty Cardiology & Vascular Diseases

Date 2021 Feb 4

PMID 33535822

Citations 4

Authors

Ami Sotokawauchi

Takanori Matsui

Yuichiro Higashimoto

Yuri Nishino

Yoshinori Koga

Minoru Yagi

Sho-Ichi Yamagishi

Affiliations

Soon will be listed here.

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.

Citing Articles

Empagliflozin ameliorates renal and metabolic derangements in obese type 2 diabetic mice by blocking advanced glycation end product-receptor axis.

Matsui T, Sotokawauchi A, Nishino Y, Koga Y, Yamagishi S Mol Med. 2025; 31(1):88.

PMID: 40050708 PMC: 11887197. DOI: 10.1186/s10020-025-01138-0.

Structures of Toxic Advanced Glycation End-Products Derived from Glyceraldehyde, A Sugar Metabolite.

Sakai-Sakasai A, Takeda K, Suzuki H, Takeuchi M Biomolecules. 2024; 14(2).

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Receptor of advanced glycation end-products axis and gallbladder cancer: A forgotten connection that we should reconsider.

Rojas A, Lindner C, Schneider I, Gonzalez I, Morales M World J Gastroenterol. 2022; 28(39):5679-5690.

PMID: 36338887 PMC: 9627425. DOI: 10.3748/wjg.v28.i39.5679.

The RAGE/DIAPH1 Signaling Axis & Implications for the Pathogenesis of Diabetic Complications.

Ramasamy R, Shekhtman A, Schmidt A Int J Mol Sci. 2022; 23(9).

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Intracellular Toxic AGEs (TAGE) Triggers Numerous Types of Cell Damage.

Takeuchi M, Sakasai-Sakai A, Takata T, Takino J, Koriyama Y, Kikuchi C Biomolecules. 2021; 11(3).

PMID: 33808036 PMC: 8001776. DOI: 10.3390/biom11030387.

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