Evidence mapPaperPMID 41183804Full record

ArticleDiabetes & metabolism journal2026

Targeting PGC-1α by miRNA-374 Simultaneously Improve β-Cell Dysfunction and Suppress Hepatic Glucose Overproduction.

Ji-Won Kim, Joonyub Lee, Young-Hye You, Chan-Hee Oh, Heon-Seok Park, Eun Young Lee, Seung-Hwan Lee, Seung-Hyun Ko, Ji-Ho Park, Kun-Ho Yoon

Abstract read
In one paragraph

Article in Diabetes & metabolism journal, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Ji-Won Kim *Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Joonyub Lee *Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Young-Hye YouDivision of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Chan-Hee OhDepartment of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
Heon-Seok ParkDivision of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Eun Young LeeDivision of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Seung-Hwan LeeDivision of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Seung-Hyun KoDivision of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Ji-Ho ParkDepartment of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
Kun-Ho YoonDivision of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Funding

Korea Health Industry Development InstituteKorean Diabetes Association 2019F-3Ministry of Health and Welfare RS-2022-KH127044Ministry of Health and Welfare RS-2024-00404132Ministry of Health and Welfare RS-2024-00408915National Research Foundation of Korea 2016R1D1A1A09918219National Research Foundation of Korea 2022R1I1A1A01068401National Research Foundation of Korea RS-2022-NR067389National Research Foundation of Korea RS-2025-00555223
6 · The paper itself

Abstract

backgruoundIn this study, we aimed to validate the potential of miR-374 in ameliorating hyperglycemia by regulating peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1α) expression in pancreatic islets and liver.

methodsTo identify miRNAs targeting PGC-1α, we performed miRNA chip analysis in rat islets under hyperglycemic and euglycemic conditions. Luciferase reporter assay was performed to identify miR binding sites in the 3'-untranslated region (3' UTR) of PGC-1α. In db/db mice, miRNA-encapsulated adenoviruses were administered and intraperitoneal glucose tolerance test and glucose stimulated insulin secretion tests were performed. For enhanced delivery to β-cells, we developed exendin-4 (Ex-4) coated cationic lipoparticles (CCLs) encapsulating miRNAs. The therapeutic potential of Ex-4-CCL-miRNA was further evaluated in insulin-producing cells derived from induced pluripotent stem cells.

resultsBy analyzing miRNA expression in primary rat islets exposed under hyperglycemic environment, we identified miR-374 as a potential target. In vitro experiments confirmed that miR-374 significantly suppressed PGC-1α expression in β-cells and hepatocytes by binding to its 3'-UTR. In vivo experiments using adenovirus-mediated miR-374 (Ad-miR-374) delivering directly to the pancreas and liver of db/db mice demonstrated improved glycemic control, enhanced insulin secretion, and downregulated hepatic gluconeogenesis-related genes (G6Pase, Pepck, PC). To enhance the clinical applicability of miR-374, we developed Ex-4-CCLs. Ex-4-CCL-miR-374 successfully alleviated hyperglycemia, restored pancreatic islet function, and decreased gluconeogenesis gene expression in db/db mice. Furthermore, Ex-4-CCL-miR-374 improved insulin secretory function in glucotoxicity-exposed human induced pluripotent stem cell-derived insulin producing cells.

conclusionBased on these findings, we propose that Ex-4-CCL-miR-374 as a promising therapeutic approach to reverse β-cell dysfunction and improve hepatic insulin resistance in type 2 diabetes mellitus.

Indexed as

GlucoseInsulin-Secreting CellsLiverMicroRNAsPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaAnimalsHumansHyperglycemiaMaleMiceRatsGlucoseMicroRNAsPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaPpargc1a protein, mousePpargc1a protein, ratDiabetes mellitus, type 2GluconeogenesisInsulin secretionIslets of LangerhansLiverMicroRNAs

Identifiers

PMID41183804
PMCPMC13175703

What Socratic holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.