Effect of Anagliptin on Vascular Injury in the Femoral Artery of Type 2 Diabetic Rats

• Published in: Biological & pharmaceutical bulletin Vol. 47; no. 1; pp. 204 - 212
• Main Authors: Noda, Masato, Kikuchi, Chigusa, Hori, Eisei, Iwao, Takahiro, Nagami, Chie, Takeuchi, Masayoshi, Matsunaga, Tamihide
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01.01.2024; Japan Science and Technology Agency
• Subjects: advanced glycation end-product; Advanced glycosylation end products; Animal models; Blood levels; diabetes mellitus; Diabetes mellitus (non-insulin dependent); Femoral artery; Femur; Glucagon; Glucagon-like peptide 1; Glucose; NAD(P)H oxidase; NADPH-diaphorase; Otsuka Long-Evans Tokushima Fatty; Oxidative stress; Veins & arteries; diabetes mellitus; Otsuka Long-Evans Tokushima Fatty; advanced glycation end-product
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b23-00706

Patients with diabetes mellitus (DM) often experience complications such as peripheral arterial disease (PAD), which is thought to be caused by vascular damage resulting from increased oxidative stress. Dipeptidyl peptidase-4 inhibitors have been reported to reduce oxidative stress, although the exact mechanism remains unclear. This study aimed to investigate the impact of long-term (6 weeks) anagliptin treatment at a dose of 200 mg/kg/d against oxidative stress in the femoral artery of Otsuka Long-Evans Tokushima Fatty (OLETF) rats using a well-established animal model for type 2 DM. Serum toxic advanced glycation end-products concentrations and blood glucose levels after glucose loading were significantly elevated in OLETF rats compared to Long-Evans Tokushima Otsuka (LETO) rats but were significantly suppressed by anagliptin administration. Plasma glucagon-like peptide-1 concentrations after glucose loading were significantly increased in anagliptin-treated rats. Superoxide production and reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity in femoral arteries were significantly increased in OLETF rats compared to LETO rats but were significantly decreased by anagliptin administration. The expressions of NADPH oxidase components (p22phox in the intima region and p22phox and gp91phox in the media region) in the femoral artery were significantly increased in OLETF rats compared to LETO rats but were significantly suppressed by anagliptin administration. Furthermore, the femoral artery showed increased wall thickness in OLETF rats compared to LETO rats, but anagliptin administration reduced the thickening. This study suggests that long-term anagliptin administration can reduce oxidative stress in femoral arteries and improve vascular injury.