Biochemical Sciences Division, Rajiv Gandhi Institute of IT and Biotechnology, Bharati Vidyapeeth (Deemed to be University), Pune, Maharashtra State, India; Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland; Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Symbiosis School of Biological Sciences (SSBS), Symbiosis International (Deemed University) (SIU), Lavale, Pune, Maharashtra State, India; Biochemical Sciences Division, Rajiv Gandhi Institute of IT and Biotechnology, Bharati Vidyapeeth (Deemed to be University), Pune, Maharashtra State, India.
Diabetes Metab Syndr. 2022 Mar;16(3):102441. doi: 10.1016/j.dsx.2022.102441. Epub 2022 Feb 24.
The secondary vascular complications in diabetes mellitus (DM) are contributed by acute as well as inflammatory responses which get activated due to interaction between glycation adducts and respective receptors.
The present work was performed to understand the relationship between Advanced glycation end products (AGEs)-receptor for advanced glycation end products (RAGE) interaction with oxidative stress and inflammation in vascular complications.
For the present work we recruited 103 controls, 200 patients with type 2 DM, and 200 patients with Diabetic complications. Different Plasma glycation adducts (fructosamine, carbonyls, AGEs, β-amyloid content, free amino groups, and free thiol groups); RAGE isoforms, level of antioxidant such as glutathione, catalase activity, nitric oxide level, total antioxidant capacity, and superoxide dismutase activity, as well as oxidative markers, and expression of Nε-carboxymethyl-lysine (CML), different isoforms of RAGE, NF-κB, and inflammatory markers were analyzed.
Glycation adducts were higher in DM patients and more elevated in nephropathy patients where free amino groups and thiol groups lowered as compared to controls. sRAGE levels and expression were increased mainly in nephropathy. CML expression was higher in nephropathy patients. The antioxidant profile indicates a reduced level of different antioxidants while increased lipid peroxidation and intracellular ROS generation in DM and much higher in nephropathy patients. Expression of membrane RAGE, NF-κB, and inflammatory markers showed a remarkably increased level in DM patients with nephropathy.
This work provides the first evidence of four different RAGE isoforms in diabetes and in complications. The glycation via the activation of RAGE, oxidative stress, and resultant inflammation plays a crucial role in the development of diabetic complications.
糖尿病（DM）的继发性血管并发症是由急性和炎症反应引起的，这些反应是由于糖化产物与相应受体之间的相互作用而激活的。
本研究旨在了解高级糖基化终产物（AGEs）-高级糖基化终产物受体（RAGE）与血管并发症中的氧化应激和炎症之间的关系。
在本研究中，我们招募了 103 名对照者、200 名 2 型糖尿病患者和 200 名糖尿病并发症患者。分析了不同的血浆糖化产物（果糖胺、羰基、AGEs、β-淀粉样蛋白含量、游离氨基基团和游离巯基基团）；RAGE 同工型、谷胱甘肽等抗氧化剂水平、过氧化氢酶活性、一氧化氮水平、总抗氧化能力和超氧化物歧化酶活性以及氧化标志物和 Nε-羧甲基赖氨酸（CML）、不同同工型的 RAGE、NF-κB 和炎症标志物的表达。
糖化产物在糖尿病患者中升高，在肾病患者中升高更为明显，与对照组相比，游离氨基基团和巯基基团降低。sRAGE 水平和表达主要在肾病中增加。CML 表达在肾病患者中较高。抗氧化谱表明不同抗氧化剂水平降低，而在糖尿病患者中脂质过氧化和细胞内 ROS 生成增加，在肾病患者中增加更为明显。膜 RAGE、NF-κB 和炎症标志物的表达在合并肾病的糖尿病患者中显示出显著增加的水平。
本研究首次提供了糖尿病及其并发症中四种不同 RAGE 同工型的证据。通过 RAGE 的激活、氧化应激和由此产生的炎症导致的糖化作用在糖尿病并发症的发展中起着至关重要的作用。
