Diabetes & Metabolism Journal

Original Articles

Pharmacotherapy
Acute Hyperinsulinemia during Hyperinsulinemic- Euglycemic Clamp Influences DNA Methylation and Gene Expression in Peripheral Blood Cells of Adult Men: Minjae Joo, Dongseong Shin, Xuan Trong Truong, Seungyoon Nam, Dae Ho Lee; Received January 25, 2025 Accepted July 1, 2025 Published online September 5, 2025; DOI: https://doi.org/10.4093/dmj.2025.0072 [Epub ahead of print]

5,353 View
34 Download

Abstract PDF Supplementary Material PubReader ePub: Background
Acute hyperinsulinemia may directly affect blood cells. In this study a hyperinsulinemic-euglycemic clamp (HEC) and multiomics methods were used to explore the epigenetic regulation by hyperinsulinemia in blood cells.
Methods
To assess short-term changes in DNA methylation (within 2 hours), blood samples were collected from five non-diabetic adults before and after HEC. mRNA sequencing (mRNA-seq) and targeted bisulfite sequencing (methyl-seq) were performed. Using mRNA-seq, 697 differentially expressed genes (DEGs) were identified, and methyl-seq was used to select those with changes in promoter or gene body methylation. In vitro validation study was also performed in THP1 and 3T3–L1 cells after acute insulin treatment.
Results
Among the 697 DEGs, 119 (henceforth, ‘methyl-DEGs’) showed methylation changes. Of these 697 DEGs, 45 (‘publictrait- DEGs’) were associated with pathways such as oxidative stress, insulin signaling, inflammation, and carbohydrate metabolism. Interaction networks between methyl-DEGs and public-trait-DEGs revealed that six genes (B3GALNT1, ESR1, FGF4, PER1, PRKAR1B, and TNFSF4) were affected by DNA methylation and linked to insulin response or diabetes. In response to acute insulin treatment, ESR1, PRKAR1B, PER1, and B3GALNT1 expression decreased in THP1 cells. Similar trends were seen in 3T3–L1 cells, except B3GALNT1. PER1 displayed consistent and significant downregulation across the clamp study and the two cell lines, indicating it as a key circadian-responsive gene under acute hyperinsulinemia.
Conclusion
These results provide epigenetic evidence for the role of DNA methylation in CpG regions and gene bodies in hyperinsulinemia- mediated regulation of gene expression in blood cells, which warrants further studies in relation to diabetes-related pathophysiology.

Complications
Association of Succinate and Adenosine Nucleotide Metabolic Pathways with Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus: Inha Jung, Seungyoon Nam, Da Young Lee, So Young Park, Ji Hee Yu, Ji A Seo, Dae Ho Lee, Nan Hee Kim; Diabetes Metab J. 2024;48(6):1126-1134. Published online July 1, 2024; DOI: https://doi.org/10.4093/dmj.2023.0377

6,150 View
165 Download
10 Web of Science
9 Crossref

Abstract PDF Supplementary Material PubReader ePub

Background
Although the prevalence of diabetic kidney disease (DKD) is increasing, reliable biomarkers for its early detection are scarce. This study aimed to evaluate the association of adenosine and succinate levels and their related pathways, including hyaluronic acid (HA) synthesis, with DKD.
Methods
We examined 235 participants and categorized them into three groups: healthy controls; those with diabetes but without DKD; and those with DKD, which was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m². We compared the concentrations of urinary adenosine, succinate, and HA and the serum levels of cluster of differentiation 39 (CD39) and CD73, which are involved in adenosine generation, among the groups with DKD or albuminuria. In addition, we performed multiple logistic regression analysis to evaluate the independent association of DKD or albuminuria with the metabolites after adjusting for risk factors. We also showed the association of these metabolites with eGFR measured several years before enrollment. This study was registered with the Clinical Research Information Service (https://cris.nih.go.kr; Registration number: KCT0003573).
Results
Urinary succinate and serum CD39 levels were higher in the DKD group than in the control and non-DKD groups. Correlation analysis consistently linked urinary succinate and serum CD39 concentrations with eGFR, albuminuria, and ΔeGFR, which was calculated retrospectively. However, among the various metabolites studied, only urinary succinate was identified as an independent indicator of DKD and albuminuria.
Conclusion
Among several potential metabolites, only urinary succinate was independently associated with DKD. These findings hold promise for clinical application in the management of DKD.

Citations

Citations to this article as recorded by

Diabetic kidney disease: integrating multi-omics insights, artificial intelligence, and novel therapeutics for precision medicine
Tao Li, Kaili Chen, Yiting Sun, Linqi Zhang
Frontiers in Genetics.2026;[Epub] CrossRef
Spatial metabolomics: A new tool for unravelling the metabolic disorders and heterogeneity in diabetic kidney disease (Review)
Hanfei Li, Yuxi Li, Bo Zhang, Wenhao Cheng, Guowei Ma, Jin Rong, Shiru Duan, Di Feng, Tingting Zhao
International Journal of Molecular Medicine.2026; 57(4): 1. CrossRef
Trifolirhizin: A Phytochemical with Multiple Pharmacological Properties
Varun Jaiswal, Hae-Jeung Lee
Molecules.2025; 30(2): 383. CrossRef
The role of redox signaling in mitochondria and endoplasmic reticulum regulation in kidney diseases
Omar Emiliano Aparicio-Trejo, Estefani Yaquelin Hernández-Cruz, Laura María Reyes-Fermín, Zeltzin Alejandra Ceja-Galicia, José Pedraza-Chaverri
Archives of Toxicology.2025; 99(5): 1865. CrossRef
Chronic succinate exposure does not cause liver injury
Joseph Balnis, Emily L. Jackson, Lisa A. Drake, Catherine E. Vincent, Hwajeong Lee, Harold A. Singer, Ariel Jaitovich
American Journal of Physiology-Endocrinology and Metabolism.2025; 329(1): E39. CrossRef
Succinate Facilitates CD4+ T Cell Infiltration and CCL1 Production to Promote Myofibroblast Activation and Renal Fibrosis in UUO Mice
Yuandong Tao, Wei Zhang, Dehong Liu, Hualin Cao, Xiaoyu Yi, Xiangling Deng, Pin Li, Xiaoli Shen, Huixia Zhou
Journal of Inflammation Research.2025; Volume 18: 7827. CrossRef
From inflammation to healing: the crucial role of GPR91 activation and SDH inhibition in chronic diabetic wound recovery
Hengdeng Liu, Shixin Zhao, Hanwen Wang, Xuefeng He, Suyue Gao, Minmin Su, Miao Zhen, Shuying Chen, Lei Chen, Julin Xie
Stem Cell Research & Therapy.2025;[Epub] CrossRef
Network pharmacology and untargeted metabolomics reveal the mechanisms of Bushen Kaixuan Tongluo formula in diabetic kidney disease
You Wang, Baosheng Zhao, Zhuqing Yang, Lingling Qin, Haiyan Wang, Cuiyan Lv, Tonghua Liu, Guangrui Huang
Journal of Chromatography B.2025; 1265: 124752. CrossRef
Oxidative Stress, Metabolic Impairment and Neuroinflammation are Associated With Target Organ Damage in SHRSP
S Hojná, L Mráziková, A Shánělová, H Pelantová, A Montezano, R Touyz, L Maletínská, J Kuneš
Physiological Research.2025; : 779. CrossRef

First
Prev
Page of 1
Next
Last

Search