Diabetes & Metabolism Journal

Original Articles

Basic and Translational Research
Inflammatory Milieu by Crosstalk between Glomerulus and Proximal Tubular Cells in Type 2 Diabetes Mellitus Kidney Disease: Peong Gang Park, Juhyeon Hwang, Yongjun Kim, Minki Hong, Donghwan Yun, Haein Yoon, Chaelin Kang, Sohyun Bae, Soo Heon Kwak, Yong Chul Kim, Kyung Chul Moon, Dong-Sup Lee, Yon Su Kim, Hee Gyung Kang, Hyun Je Kim, Seung Seok Han; Diabetes Metab J. 2025;49(5):1024-1039. Published online March 31, 2025; DOI: https://doi.org/10.4093/dmj.2024.0535

6,557 View
271 Download
6 Web of Science
7 Crossref

Abstract PDF Supplementary Material PubReader ePub

Background
Due to the limited availability of therapeutic agents for type 2 diabetic kidney disease (T2DKD), there is a need for further knowledge derived from experimental models and innovative techniques. In addressing this issue, single-cell RNA sequencing (scRNA-seq) has been exclusively applied to a genetically modified diabetic kidney disease model, but not to an induced model representing T2DKD. Herein, we analyzed scRNA-seq and other experiments from an induced T2DKD model and validated the results in human-derived biospecimens.
Methods
The model was induced by combining a high-fat diet with streptozotocin to simulate induced T2DKD. scRNA-seq, histological, and flow cytometric analyses were conducted, and the results were compared with control mice. The findings were then applied to human T2DKD kidneys.
Results
Biochemical and histological analyses unveiled early-stage T2DKD features, such as hyperfiltration, increased proteinuria, glomerulomegaly, and interstitial fibrosis. scRNA-seq identified that proximal tubules secreted a variety of chemokines, potentially in response to crosstalk with glomeruli. Notably, C-X-C motif chemokine 12 (CXCL12) emerged as a key player in potentially promoting T-cell recruitment. Flow cytometry substantiated T-cell infiltration into the kidney of the T2DKD model. This finding was further corroborated in human biopsied kidney tissues, showing a correlation between elevated CXCL12 levels and T2DKD progression.
Conclusion
The induced T2DKD model highlights the pivotal role of CXCL12-mediated T-cell infiltration, stemming from the crosstalk between proximal tubules and glomeruli. This data serves as a foundation for future studies, promising a therapeutic target for T2DKD.

Citations

Citations to this article as recorded by

Inflammation and Diabetic Kidney Disease
Rong Mei Zhang, Maria Luiza Caramori
International Journal of Molecular Sciences.2026; 27(2): 1097. CrossRef
Research progress in single‑cell omics technologies for kidney disease (Review)
Jia Xu, Ziwei Chen, Shengyao Li, Xiaoya Wang, Ming Chen
International Journal of Molecular Medicine.2026; 57(5): 1. CrossRef
SFRP2 aggravates diabetic kidney disease by repressing the renal protective CH25H/25-hydroxycholesterol axis in mesangial cells
Dan Lv, Ziyue Lin, Jiakun Yang, Wuchao Li, Keqian Wu, Rui Peng, Handeng Liu, He Zha, Xiong Zhong Ruan, Xiaohui Liao, Yan Sun, Zheng Zhang
Journal of Advanced Research.2026;[Epub] CrossRef
Qiling Hushen Formula Ameliorates Type 2 Diabetic Kidney Disease via Gut‐Kidney Axis Restoration and TLR4/NF‐κB/NLRP3 Suppression
Yuxin Wang, Pei Sheng, Xue Wang, Min Lin, Wentao Cai, Shiyao Wei, Yuyun Du, Ming Yan, Lei Wang, Xiaofei An, Haoqiang Zhang
Journal of Diabetes Research.2026;[Epub] CrossRef
Efficacy and safety of jinlida granule in the treatment of diabetic kidney disease: a systematic review and meta-analysis of randomized controlled trials
Qi Yong, Yunxi Xu, Peiying Zhang, Hua Bai, Chao Xu, Hejiang Ye
Frontiers in Pharmacology.2026;[Epub] CrossRef
Glomerulo–Tubular Crosstalk in Diabetic Kidney Disease: From Pathophysiology to Novel Therapeutics
Il Young Kim
Electrolytes & Blood Pressure.2026; 24(2): 106. CrossRef
Aging Mediates Inflammatory Transformation of Kidney-Resident Macrophages via Thrombospondin-1 Signaling
Chaelin Kang, Donghwan Yun, Boyoun Jang, Yongjun Kim, Minki Hong, Juhyeon Hwang, Haein Yoon, Jeongmin Oh, Hyun Mu Shin, Kyung Chul Moon, Dong-Sup Lee, Yon Su Kim, Hyun Je Kim, Seung Seok Han
Immune Network.2025;[Epub] CrossRef

Basic and Translational Research
Revealing VCAN as a Potential Common Diagnostic Biomarker of Renal Tubules and Glomerulus in Diabetic Kidney Disease Based on Machine Learning, Single-Cell Transcriptome Analysis and Mendelian Randomization: Li Jiang, Jie Jian, Xulin Sai, Xiai Wu; Diabetes Metab J. 2025;49(3):407-420. Published online January 24, 2025; DOI: https://doi.org/10.4093/dmj.2024.0233

9,535 View
399 Download
3 Web of Science
3 Crossref

Abstract PDF Supplementary Material PubReader ePub

Background
Diabetic kidney disease (DKD) is recognized as a significant complication of diabetes mellitus and categorized into glomerular DKDs and tubular DKDs, each governed by distinct pathological mechanisms and biomarkers.
Methods
Through the identification of common features observed in glomerular and tubular lesions in DKD, numerous differentially expressed gene were identified by the machine learning, single-cell transcriptome and mendelian randomization.
Results
The diagnostic markers versican (VCAN) was identified, offering supplementary options for clinical diagnosis. VCAN significantly highly expressed in glomerular parietal epithelial cell and proximal convoluted tubular cell. It was mainly involved in the up-regulation of immune genes and infiltration of immune cells like mast cell. Mendelian randomization analysis confirmed that serum VCAN protein levels were a risky factor for DKD, while there was no reverse association. It exhibited the good diagnostic potential for estimated glomerular filtration rate and proteinuria in DKD.
Conclusion
VCAN showed the prospects into DKD pathology and clinical indicator.

Citations

Citations to this article as recorded by

Transient versican expression is required for β1-integrin accumulation during podocyte layer morphogenesis in amphibian developing kidney
Isabelle Buisson, Jean-François Riou, Muriel Umbhauer, Ronan Le Bouffant, Valérie Bello
Cells & Development.2026; 185: 204062. CrossRef
m6A Modified VCAN Promotes Glomerular Endothelial Cells Injury and Diabetic Nephropathy by SHH Pathway
Jie Jiang, Jicheng Zhang, Chao Wang, Feng Wang
Applied Biochemistry and Biotechnology.2026; 198(5): 3461. CrossRef
Multi-omics and machine learning identify FN1 and ALDH2 as diagnostic biomarkers and therapeutic targets in early and late diabetic kidney disease
Jingwei Lin, Yingying Zheng, Diman Mai, Fuxiang Fang, Zhuokun Wei, Mengyu Liu, Trung Hieu Pham, Ming Li, Jiawen Zhao
Renal Failure.2025;[Epub] CrossRef

Basic Research
Single-Cell Landscape and a Macrophage Subset Enhancing Brown Adipocyte Function in Diabetes: Junfei Gu, Jiajia Jin, Xiaoyu Ren, Xinjie Zhang, Jiaxuan Li, Xiaowei Wang, Shucui Zhang, Xianlun Yin, Qunye Zhang, Zhe Wang; Diabetes Metab J. 2024;48(5):885-900. Published online May 29, 2024; DOI: https://doi.org/10.4093/dmj.2023.0278

10,138 View
311 Download
1 Web of Science
3 Crossref

Abstract PDF Supplementary Material PubReader ePub

Background
Metabolic dysregulation is a hallmark of type 2 diabetes mellitus (T2DM), in which the abnormalities in brown adipose tissue (BAT) play important roles. However, the cellular composition and function of BAT as well as its pathological significance in diabetes remain incompletely understood. Our objective is to delineate the single-cell landscape of BAT-derived stromal vascular fraction (SVF) and their characteristic alterations in T2DM rats.
Methods
T2DM was induced in rats by intraperitoneal injection of low-dose streptozotocin and high-fat diet feeding. Single-cell mRNA sequencing was then performed on BAT samples and compared to normal rats to characterize changes in T2DM rats. Subsequently, the importance of key cell subsets in T2DM was elucidated using various functional studies.
Results
Almost all cell types in the BAT-derived SVF of T2DM rats exhibited enhanced inflammatory responses, increased angiogenesis, and disordered glucose and lipid metabolism. The multidirectional differentiation potential of adipose tissue-derived stem cells was also reduced. Moreover, macrophages played a pivotal role in intercellular crosstalk of BAT-derived SVF. A novel Rarres2+macrophage subset promoted the differentiation and metabolic function of brown adipocytes via adipose-immune crosstalk.
Conclusion
BAT SVF exhibited strong heterogeneity in cellular composition and function and contributed to T2DM as a significant inflammation source, in which a novel macrophage subset was identified that can promote brown adipocyte function.

Citations

Citations to this article as recorded by

Single-Cell Landscape and a Macrophage Subset Enhancing Brown Adipocyte Function in Diabetes (Diabetes Metab J 2024;48:885-900)
Yea Eun Kang, Ju Hee Lee
Diabetes & Metabolism Journal.2025; 49(1): 160. CrossRef
Single-Cell Landscape and a Macrophage Subset Enhancing Brown Adipocyte Function in Diabetes (Diabetes Metab J 2024;48:885-900)
Junfei Gu, Xinjie Zhang, Qunye Zhang, Zhe Wang
Diabetes & Metabolism Journal.2025; 49(1): 162. CrossRef
Engineered stromal vascular fraction for tissue regeneration
Jianfeng Liu, Yiwei Li, Yanan Zhang, Zhiwei Zhao, Bin Liu
Frontiers in Pharmacology.2025;[Epub] CrossRef

Review

Basic Research
Heterogeneity of Islet Cells during Embryogenesis and Differentiation: Shugo Sasaki, Takeshi Miyatsuka; Diabetes Metab J. 2023;47(2):173-184. Published online January 12, 2023; DOI: https://doi.org/10.4093/dmj.2022.0324

11,306 View
336 Download
7 Web of Science
7 Crossref

Abstract PDF PubReader ePub

Diabetes is caused by insufficient insulin secretion due to β-cell dysfunction and/or β-cell loss. Therefore, the restoration of functional β-cells by the induction of β-cell differentiation from embryonic stem (ES) and induced-pluripotent stem (iPS) cells, or from somatic non-β-cells, may be a promising curative therapy. To establish an efficient and feasible method for generating functional insulin-producing cells, comprehensive knowledge of pancreas development and β-cell differentiation, including the mechanisms driving cell fate decisions and endocrine cell maturation is crucial. Recent advances in single-cell RNA sequencing (scRNA-seq) technologies have opened a new era in pancreas development and diabetes research, leading to clarification of the detailed transcriptomes of individual insulin-producing cells. Such extensive high-resolution data enables the inference of developmental trajectories during cell transitions and gene regulatory networks. Additionally, advancements in stem cell research have not only enabled their immediate clinical application, but also has made it possible to observe the genetic dynamics of human cell development and maturation in a dish. In this review, we provide an overview of the heterogeneity of islet cells during embryogenesis and differentiation as demonstrated by scRNA-seq studies on the developing and adult pancreata, with implications for the future application of regenerative medicine for diabetes.

Citations

Citations to this article as recorded by

CK19 and PDX1 as Markers of Differentiation and Maturation of Pancreatic Islet Endocrine Cells
A. E. Proshchina, Yu. S. Krivova, A. S. Kharlamova, G. A. Sonin, S. V. Saveliev
Bulletin of Experimental Biology and Medicine.2026; 180(4): 487. CrossRef
Pancreatic β-cell remodeling in health and aging: Lessons from rodents and humans
Radwan Darwish, Yasmine Alcibahy, Sangeeta Dhawan, Alexandra E. Butler, Abu Saleh Md Moin
Ageing Research Reviews.2025; 110: 102815. CrossRef
Single-cell RNA sequencing in studies of type 1 diabetes mellitus: modern state-of-the-art and technical peculiarities
Azat Vadimovich Abdullatypov, Olga Valentinovna Glushkova, Ekaterina Sergeevna Petriaikina, Viktor Pavlovich Bogdanov, Dmitry Vyacheslavovich Tabakov, Vasilii Eduardovich Akimov, Vladimir Sergeevich Yudin, Anton Arturovich Keskinov, Sergey Mikhailovich Yu
Frontiers in Endocrinology.2025;[Epub] CrossRef
Imeglimin enhances α-to-β reprograming mediated by PDX1 in β-cell ablated islets
Rei Fujishima, Tomomi Taguchi, Naoya Shimizu, Agena Suzuki, Wataru Hagiwara, Shiori Ito, Satomi Takebe, Mitsuko Inoue, Takeshi Miyatsuka
Biochemical and Biophysical Research Communications.2025; 790: 152886. CrossRef
Transcriptional and temporal heterogeneity of developing α cells revealed by single-cell RNA sequencing
Naoya Shimizu, Tomomi Taguchi, Miwa Himuro, Iichiro Shimomura, Francis C. Lynn, Hirotaka Watada, Shugo Sasaki, Takeshi Miyatsuka
Biochemical and Biophysical Research Communications.2025; 792: 152996. CrossRef
Investigation of the motif activity of transcription regulators in pancreatic β-like cell subpopulations differentiated from human induced pluripotent stem cells
Eric Leclerc, Mikhail Pachkov, Lisa Morisseau, Fumiya Tokito, Cecile Legallais, Rachid Jellali, Masaki Nishikawa, Amar Abderrahmani, Yasuyuki Sakai
Molecular Omics.2024; 20(10): 654. CrossRef
Newly discovered knowledge pertaining to glucagon and its clinical applications
Dan Kawamori, Shugo Sasaki
Journal of Diabetes Investigation.2023; 14(7): 829. CrossRef

Original Articles

Obesity and Metabolic Syndrome
Regulating Hypothalamus Gene Expression in Food Intake: Dietary Composition or Calorie Density?: Mi Jang, So-Young Park, Yong-Woon Kim, Seung-Pil Jung, Jong-Yeon Kim; Diabetes Metab J. 2017;41(2):121-127. Published online December 16, 2016; DOI: https://doi.org/10.4093/dmj.2017.41.2.121

8,348 View
43 Download
5 Web of Science
5 Crossref

Abstract PDF PubReader ePub

Background

The proportion of saturated fatty acids/unsaturated fatty acids in the diet seems to act as a physiological regulation on obesity, cardiovascular diseases, and diabetes. Differently composed fatty acid diets may induce satiety of the hypothalamus in different ways. However, the direct effect of the different fatty acid diets on satiety in the hypothalamus is not clear.

Methods

Three experiments in mice were conducted to determine whether: different compositions of fatty acids affects gene mRNA expression of the hypothalamus over time; different types of fatty acids administered into the stomach directly affect gene mRNA expression of the hypothalamus; and fat composition changes in the diet affects gene mRNA expression of the hypothalamus.

Results

The type of fat in cases of purified fatty acid administration directly into the stomach may cause changes of gene expressions in the hypothalamus. Gene expression by dietary fat may be regulated by calorie amount ingested rather than weight amount or type of fat.

Conclusion

Therefore, the calorie density factor of the diet in regulating hypothalamic gene in food intake may be detrimental, although the possibility of type of fat cannot be ruled out.

Citations

Citations to this article as recorded by

γ-aminobutyric acid improves gut-brain axis function and behavioral adaptation in broilers under low-protein diet
Randi Randi, Anisa Aulia, Muhtadin Muhtadin, Chusnul Hanim, Michael T. Kidd, Muhsin Al Anas
Poultry Science.2026; 105(1): 106085. CrossRef
Prepartum fatty acid supplementation in sheep. III. Effect of eicosapentaenoic acid and docosahexaenoic acid during finishing on performance, hypothalamus gene expression, and muscle fatty acids composition in lambs1
Ana Cristina Carranza Martin, Danielle Nicole Coleman, Lyda Guadalupe Garcia, Cecilia C Furnus, Alejandro E Relling
Journal of Animal Science.2018; 96(12): 5300. CrossRef
Acute anti‐obesity effects of intracerebroventricular 11β‐HSD1 inhibitor administration in diet‐induced obese mice
M. Seo, S. A. Islam, S.‐S. Moon
Journal of Neuroendocrinology.2018;[Epub] CrossRef
Letter: Regulating Hypothalamus Gene Expression in Food Intake: Dietary Composition or Calorie Density? (Diabetes Metab J 2017;41:121-7)
Bo Kyung Koo
Diabetes & Metabolism Journal.2017; 41(3): 223. CrossRef
Response: Regulating Hypothalamus Gene Expression in Food Intake: Dietary Composition or Calorie Density? (Diabetes Metab J2017;41:121-7)
Mi Jang, So-Young Park, Yong-Woon Kim, Seung-Pil Jung, Jong-Yeon Kim
Diabetes & Metabolism Journal.2017; 41(3): 225. CrossRef

Pathophysiology
Investigating Susceptibility to Diabetes Using Features of the Adipose Tissue in Response to In Utero Polycyclic Aromatic Hydrocarbons Exposure: Worlanyo E. Gato, Daniel A. Hunter, Shamaya L. Whitby, Christopher A. Mays, Wilson Yau; Diabetes Metab J. 2016;40(6):494-508. Published online August 12, 2016; DOI: https://doi.org/10.4093/dmj.2016.40.6.494

7,643 View
108 Download
8 Web of Science
5 Crossref

Abstract PDF Supplementary Material PubReader ePub

Background

In recent times, there has been an increase in the incidence of type 2 diabetes mellitus (T2DM) particularly in children. Adipocyte dysfunction provide a critical link between obesity and insulin resistance resulting in diabetes outcome. Further, environmental chemical exposure during early years of life might be a significant contributing factor to the increase in the incidence of T2DM. This study tests the idea that exposure to environmental contaminants (2-aminoanthracene [2AA]) in utero will show effects in the adipose tissue (AT) that signify T2DM vulnerability. 2AA is a polycyclic aromatic hydrocarbon found in a variety of products.

Methods

To accomplish the study objective, pregnant dams were fed various amounts of 2AA adulterated diets from gestation through postnatal period. The neonates and older offspring were analyzed for diabetic-like genes in the ATs and analysis of serum glucose. Furthermore, weight monitoring, histopathology and immunohistochemical (IHC) staining for CD68 in AT, adipocyte size determination and adiponectin amounts in serum were undertaken.

Results

Up-regulation of adiponectin and interleukin-6 genes were noted in the pups and older rats. Combination of intrauterine 2AA toxicity with moderate high fat diet exhibited gene expression patterns similar to those of the neonates. Elevated serum glucose levels were noted in treated groups. IHC of the AT indicated no significant malformations; however, CD68+ cells were greater in the animals treated to 2AA. Similarly, mean sizes of the adipocytes were larger in treated and combined 2AA and moderate high fat animals. Adiponectin was reduced in 2AA groups.

Conclusion

From the preceding, it appears intrauterine 2AA disturbance, when combined with excess fat accumulation will lead to greater risk for the diabetic condition.

Citations

Citations to this article as recorded by

The Role of Persistent Organic Pollutants in Obesity: A Review of Laboratory and Epidemiological Studies
Jan Aaseth, Dragana Javorac, Aleksandra Djordjevic, Zorica Bulat, Anatoly Skalny, Irina Zaitseva, Michael Aschner, Alexey Tinkov
Toxics.2022; 10(2): 65. CrossRef
The Association between Urinary Polycyclic Aromatic Hydrocarbons Metabolites and Type 2 Diabetes Mellitus
Xue Wang, Ang Li, Qun Xu
International Journal of Environmental Research and Public Health.2022; 19(13): 7605. CrossRef
Dietary ingestion of 2-aminoanthracene (2AA) and the risk for type-1 diabetes (T1D)
Isaiah Seise, Zachary A. Pilz, Moses Yeboah Kusi, Bethany Bogan, Brittany Jean McHale, Worlanyo E. Gato
Journal of Environmental Science and Health, Part A.2020; 55(14): 1638. CrossRef
Association of the IL6 Gene Polymorphism with Component Features of Metabolic Syndrome in Obese Subjects
Elham Barati, Hamideh Ghazizadeh, Fatemeh Sadabadi, Elham Kazemi, Gordon A. Ferns, Amir Avan, Majid Ghayour-Mobarhan
Biochemical Genetics.2019; 57(5): 695. CrossRef
The hepatic effects in dams that ingested 2-aminoanthracene during gestation and lactation
Raven E Ulieme, Surjania Awer, John C Stagg, Wilson Yau, Worlanyo E Gato
Toxicology and Industrial Health.2019; 35(9): 568. CrossRef

First
Prev
Page of 1
Next
Last

Search