Diabetes & Metabolism Journal

Review

Pathophysiology
Protein Arginine Methyltransferases: Emerging Targets in Cardiovascular and Metabolic Disease: Yan Zhang, Shibo Wei, Eun-Ju Jin, Yunju Jo, Chang-Myung Oh, Gyu-Un Bae, Jong-Sun Kang, Dongryeol Ryu; Diabetes Metab J. 2024;48(4):487-502. Published online July 24, 2024; DOI: https://doi.org/10.4093/dmj.2023.0362

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Cardiovascular diseases (CVDs) and metabolic disorders stand as formidable challenges that significantly impact the clinical outcomes and living quality for afflicted individuals. An intricate comprehension of the underlying mechanisms is paramount for the development of efficacious therapeutic strategies. Protein arginine methyltransferases (PRMTs), a class of enzymes responsible for the precise regulation of protein methylation, have ascended to pivotal roles and emerged as crucial regulators within the intrinsic pathophysiology of these diseases. Herein, we review recent advancements in research elucidating on the multifaceted involvements of PRMTs in cardiovascular system and metabolic diseases, contributing significantly to deepen our understanding of the pathogenesis and progression of these maladies. In addition, this review provides a comprehensive analysis to unveil the distinctive roles of PRMTs across diverse cell types implicated in cardiovascular and metabolic disorders, which holds great potential to reveal novel therapeutic interventions targeting PRMTs, thus presenting promising perspectives to effectively address the substantial global burden imposed by CVDs and metabolic disorders.

Citations

Citations to this article as recorded by

Protein Arginine Methyltransferase 1: A Multi-Purpose Player in the Development of Cancer and Metabolic Disease
Daphne de Korte, Menno Hoekstra
Biomolecules.2025; 15(2): 185. CrossRef
Arginine Methylation by PRMT1 Affects ADAMTS13 Secretion and Enzymatic Activity
Szumam Liu, Min Ma, Jun Qu, Joshua Muia, Zhijian Wu, Quintijn Bonnez, Karen Vanhoorelbeke, Liang Zheng, Xinyang Zhao, X. Long Zheng
Arteriosclerosis, Thrombosis, and Vascular Biology.2025; 45(4): 506. CrossRef
Protein Arginine N‐Methyltransferase 4 Activation Contributes to Glucose‐Induced Skeletal Muscle Atrophy
Pawan Kumar, Farah Gulzar, Nikita Chhikara, Arvind K. Maurya, Sushmita Singh, Ishbal Ahmad, Sanjeev Kanojiya, Akhilesh K. Tamrakar
The FASEB Journal.2025;[Epub] CrossRef
PRMT1 in Health and Disease: Emerging Perspectives From Molecular Mechanisms to Therapeutic Strategies
Yanqun Luo, Ying Gao, Xiaoliang Deng, Lei Wang, Tao Wu
MedComm.2025;[Epub] CrossRef

Original Article

Basic Research
CycloZ Improves Hyperglycemia and Lipid Metabolism by Modulating Lysine Acetylation in KK-Ay Mice: Jongsu Jeon, Dohyun Lee, Bobae Kim, Bo-Yoon Park, Chang Joo Oh, Min-Ji Kim, Jae-Han Jeon, In-Kyu Lee, Onyu Park, Seoyeong Baek, Chae Won Lim, Dongryeol Ryu, Sungsoon Fang, Johan Auwerx, Kyong-Tai Kim, Hoe-Yune Jung; Diabetes Metab J. 2023;47(5):653-667. Published online April 26, 2023; DOI: https://doi.org/10.4093/dmj.2022.0244

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Abstract PDF Supplementary Material PubReader ePub

Background
CycloZ, a combination of cyclo-His-Pro and zinc, has anti-diabetic activity. However, its exact mode of action remains to be elucidated.
Methods
KK-Ay mice, a type 2 diabetes mellitus (T2DM) model, were administered CycloZ either as a preventive intervention, or as a therapy. Glycemic control was evaluated using the oral glucose tolerance test (OGTT), and glycosylated hemoglobin (HbA1c) levels. Liver and visceral adipose tissues (VATs) were used for histological evaluation, gene expression analysis, and protein expression analysis.
Results
CycloZ administration improved glycemic control in KK-Ay mice in both prophylactic and therapeutic studies. Lysine acetylation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, liver kinase B1, and nuclear factor-κB p65 was decreased in the liver and VATs in CycloZ-treated mice. In addition, CycloZ treatment improved mitochondrial function, lipid oxidation, and inflammation in the liver and VATs of mice. CycloZ treatment also increased the level of β-nicotinamide adenine dinucleotide (NAD⁺), which affected the activity of deacetylases, such as sirtuin 1 (Sirt1).
Conclusion
Our findings suggest that the beneficial effects of CycloZ on diabetes and obesity occur through increased NAD⁺ synthesis, which modulates Sirt1 deacetylase activity in the liver and VATs. Given that the mode of action of an NAD+ booster or Sirt1 deacetylase activator is different from that of traditional T2DM drugs, CycloZ would be considered a novel therapeutic option for the treatment of T2DM.

Citations

Citations to this article as recorded by

Beneficial Effects of a Novel Fructose-1,6-Bisphosphatase Inhibitor Cpd96 on Insulin Secretion in Type 2 Diabetes
Kejia Xu, Jiaxuan Zhao, Liran Lei, Quan Liu, Hui Cao, Caina Li, Yi Huan, Xinqian Geng, Lin Zhang, Xi Cao, Ying Yang, Yongzhao Mu, Rongcui Li, Zhufang Shen, Lei Lei, Shuainan Liu
ACS Pharmacology & Translational Science.2026; 9(1): 153. CrossRef
Combined Histidine and Proline Supplementation (HISPRO) Enhances Oxidative and Mitochondrial Function in Skeletal Muscle Through SIRT1-Associated Signaling
Dohyun Lee, Jongsu Jeon, Gyuwon Huh, Seoyeong Baek, Daehun Kim, Hyeon-Ji Kang, Hoyul Lee, In-Kyu Lee, Jae-Han Jeon, Hoe-Yune Jung
Cells.2026; 15(10): 887. CrossRef
Microwave Pretreatment-Induced Significant Nutrient and Metabolite Changes in Sea Cucumber Apostichopus japonicus
Dairong Song, Fang Liu, Airong Jia, Xue Liu, Tingting Cui, Hui Zhang, Miansong Zhang
Marine Drugs.2025; 23(6): 249. CrossRef
Distinct types of protein modifications in diabetic endothelial dysfunction
Qianyou Zhou, Xintong Ge, Zhaojing Chen, Danyi Cao, Yun Chen, Jiahai Shi, Guoliang Meng
Cardiovascular Diabetology.2025;[Epub] CrossRef
Cyclo His‐Pro Attenuates Muscle Degeneration in Murine Myopathy Models
Alessia De Masi, Nadège Zanou, Keno Strotjohann, Dohyun Lee, Tanes I. Lima, Xiaoxu Li, Jongsu Jeon, Nicolas Place, Hoe‐Yune Jung, Johan Auwerx
Advanced Science.2024;[Epub] CrossRef
CycloZ Suppresses TLR4-Driven Inflammation to Reduce Asthma-Like Responses in HDM-Exposed Mouse Models
Dohyun Lee, Jongsu Jeon, Seoyeong Baek, Onyu Park, Ah-Ram Kim, Myoung-Sool Do, Hoe-Yune Jung
Cells.2024; 13(23): 2034. CrossRef
Cyclic Peptides as Protein Kinase Modulators and Their Involvement in the Treatment of Diverse Human Diseases
Lorena Martínez-Alcantar, Laura Hernández-Padilla, Alma Laura Díaz-Pérez, Lizbeth Guadalupe Villalón-Magallán, Mayra Xóchitl Durán-Maldonado, César Díaz-Pérez, Marlene E. Campos-Morales, Citlali Figueroa-Guzmán, Jesús Campos-García
Kinases and Phosphatases.2024; 2(4): 346. CrossRef

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