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

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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
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

Others
Clinical Trial Protocol for Porcine Islet Xenotransplantation in South Korea: Byung-Joon Kim, Jun-Seop Shin, Byoung-Hoon Min, Jong-Min Kim, Chung-Gyu Park, Hee-Jung Kang, Eung Soo Hwang, Won-Woo Lee, Jung-Sik Kim, Hyun Je Kim, Iov Kwon, Jae Sung Kim, Geun Soo Kim, Joonho Moon, Du Yeon Shin, Bumrae Cho, Heung-Mo Yang, Sung Joo Kim, Kwang-Won Kim; Diabetes Metab J. 2024;48(6):1160-1168. Published online May 21, 2024; DOI: https://doi.org/10.4093/dmj.2023.0260

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Abstract PDF Supplementary Material PubReader ePub

Background
Islet transplantation holds promise for treating selected type 1 diabetes mellitus patients, yet the scarcity of human donor organs impedes widespread adoption. Porcine islets, deemed a viable alternative, recently demonstrated successful longterm survival without zoonotic risks in a clinically relevant pig-to-non-human primate islet transplantation model. This success prompted the development of a clinical trial protocol for porcine islet xenotransplantation in humans.
Methods
A single-center, open-label clinical trial initiated by the sponsor will assess the safety and efficacy of porcine islet transplantation for diabetes patients at Gachon Hospital. The protocol received approval from the Gachon Hospital Institutional Review Board (IRB) and the Korean Ministry of Food and Drug Safety (MFDS) under the Investigational New Drug (IND) process. Two diabetic patients, experiencing inadequate glycemic control despite intensive insulin treatment and frequent hypoglycemic unawareness, will be enrolled. Participants and their family members will engage in deliberation before xenotransplantation during the screening period. Each patient will receive islets isolated from designated pathogen-free pigs. Immunosuppressants and systemic infection prophylaxis will follow the program schedule. The primary endpoint is to confirm the safety of porcine islets in patients, and the secondary endpoint is to assess whether porcine islets can reduce insulin dose and the frequency of hypoglycemic unawareness.
Conclusion
A clinical trial protocol adhering to global consensus guidelines for porcine islet xenotransplantation is presented, facilitating streamlined implementation of comparable human trials worldwide.

Citations

Citations to this article as recorded by

Present Advances and Emerging Challenges in Kidney Xenotransplantation
Kazuaki Yamanaka, Yoichi Kakuta, Shuji Miyagawa, Kentaro Inoue, Soichi Matsumura, Shota Fukae, Masataka Kawamura, Shigeaki Nakazawa, Kenichi Kobayashi, Susumu Kageyama, Norio Nonomura
Journal of Clinical Medicine.2026; 15(5): 1692. CrossRef
Allogeneic Islet Transplantation: Chronicle of a Death Foretold?
Thierry Berney, Olivier Thaunat, Ekaterine Berishvili
Transplant International.2025;[Epub] CrossRef
Donor pigs for clinical islet xenotransplantation: Review and future directions
Shinichi Matsumoto, Sadaki Asari, Yoshihide Nanno, Hiroyuki Nakamura, Taisuke Okawa, Takumi Fukumoto
Cell Transplantation.2025;[Epub] CrossRef
Harmonizing International Regulatory Standards for Porcine Endogenous Retrovirus (PERV) Screening in Genetically Modified Porcine Donors for First‐in‐Human Pancreatic Islet Xenotransplantation
Muhammad Umer Suleman, Muhammad Mursaleen, Umer Khalil
Xenotransplantation.2025;[Epub] CrossRef

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