Evidence map›Paper›PMID 41389876›Full record

ArticleCellular and molecular gastroenterology and hepatology2026

DOCK10 Regulates Insulin Hypersecretion in Insulinoma and Serves as a Diagnostic and Therapeutic Target.

Hiromune Katsuda, Go Ito, Franziska Kimmig, Tomohiro Muto, Neha Mishra, Joana Pimenta Bernardes, Yui Hiraguri, Hironari Yamashita, Akira Ito, Yuko Kinowaki and 19 more

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Article in Cellular and molecular gastroenterology and hepatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

29 authors.

Hiromune KatsudaDepartment of Gastroenterology and Hepatology, Institute of Science Tokyo, Tokyo, Japan.
Go ItoThe Center for Personalized Medicine for Healthy Aging, Institute of Science Tokyo, Tokyo, Japan. Electronic address: gito.gast@tmd.ac.jp.
Franziska KimmigInstitute of Clinical Molecular Biology, Christian-Albrechts-University and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Tomohiro MutoDepartment of Gastroenterology and Hepatology, Institute of Science Tokyo, Tokyo, Japan.
Neha MishraInstitute of Clinical Molecular Biology, Christian-Albrechts-University and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Joana Pimenta BernardesInstitute of Clinical Molecular Biology, Christian-Albrechts-University and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Yui HiraguriDepartment of Gastroenterology and Hepatology, Institute of Science Tokyo, Tokyo, Japan.
Hironari YamashitaDepartment of Hepatobiliary and Pancreatic Surgery, Institute of Science Tokyo, Tokyo, Japan.
Akira ItoDepartment of Hepatobiliary and Pancreatic Surgery, Institute of Science Tokyo, Tokyo, Japan.
Yuko KinowakiDepartment of Comprehensive Pathology, Institute of Science Tokyo, Tokyo, Japan.
Takahiro ShinDepartment of Gastroenterology and Hepatology, Institute of Science Tokyo, Tokyo, Japan.
Satoru FujiiDepartment of Gastroenterology and Hepatology, Institute of Science Tokyo, Tokyo, Japan.
Masato MiyoshiDepartment of Gastroenterology and Hepatology, Institute of Science Tokyo, Tokyo, Japan.
Masanori KobayashiDepartment of Gastroenterology and Hepatology, Institute of Science Tokyo, Tokyo, Japan.
Daisuke AsanoDepartment of Hepatobiliary and Pancreatic Surgery, Institute of Science Tokyo, Tokyo, Japan.
Yoshiya IshikawaDepartment of Hepatobiliary and Pancreatic Surgery, Institute of Science Tokyo, Tokyo, Japan.
Hiroki UedaDepartment of Hepatobiliary and Pancreatic Surgery, Institute of Science Tokyo, Tokyo, Japan.
Keiichi AkahoshiDepartment of Hepatobiliary and Pancreatic Surgery, Institute of Science Tokyo, Tokyo, Japan.
Eriko KatsutaDepartment of Hepatobiliary and Pancreatic Surgery, Institute of Science Tokyo, Tokyo, Japan.
Yoshihito KanoDepartment of Gastroenterology and Hepatology, Institute of Science Tokyo, Tokyo, Japan; Department of Medical Oncology, Institute of Science Tokyo, Tokyo, Japan.
Shiro YuiCenter for Stem Cell and Regenerative Medicine, Institute of Science Tokyo, Tokyo, Japan.
Yasuhiro NemotoDepartment of Gastroenterology and Hepatology, Institute of Science Tokyo, Tokyo, Japan.
Atsushi KudoDepartment of Clinical Quality and Safety, Institute of Science Tokyo, Tokyo, Japan.
Daisuke BanDepartment of Hepatobiliary and Pancreatic Surgery, Institute of Science Tokyo, Tokyo, Japan.
Yasuhiro AsahinaDepartment of Gastroenterology and Hepatology, Institute of Science Tokyo, Tokyo, Japan.
Stefan SchreiberInstitute of Clinical Molecular Biology, Christian-Albrechts-University and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany; Department of Internal Medicine I, Christian-Albrechts-University and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Mamoru WatanabeOrganoid Center, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
Philip RosenstielInstitute of Clinical Molecular Biology, Christian-Albrechts-University and University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Ryuichi OkamotoDepartment of Gastroenterology and Hepatology, Institute of Science Tokyo, Tokyo, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND &

aimsInsulinomas are rare pancreatic neuroendocrine neoplasms (pan-NENs) characterized by inappropriate insulin secretion. Despite advances in imaging techniques, the reliable identification of insulin-secreting lesions remains challenging. In addition, medical treatment options are limited and have seen little development in recent years, highlighting the unmet need for improved diagnostic tools and therapeutic strategies. This study aimed to identify the molecular mechanisms underlying insulin hypersecretion in insulinomas.

methodsWe established a biobank of human insulinoma surgical specimens and matched organoids. Comprehensive transcriptomic analyses-including bulk RNA sequencing, single-cell RNA sequencing, quantitative polymerase chain reaction, and immunohistochemistry-were conducted to identify genes enriched in insulin-secreting components. Functional validation was performed using MIN6 cells, a xenograft mouse model, and long-term cultured human insulinoma organoids.

resultsWe identified dedicator of cytokinesis 10 (DOCK10) as a gene selectively overexpressed in insulin-secreting components of insulinomas. DOCK10 knockdown impaired glucose-stimulated insulin secretion in both mouse insulinoma cells and patient-derived organoids. Inhibition of the downstream effector Cdc42 with ML141 reduced insulin hypersecretion and improved survival in a MIN6 xenograft mouse model. These findings uncover a previously unrecognized role of the DOCK10-Cdc42 axis in regulating insulin secretion in insulinoma.

conclusionsThis study suggests that DOCK10 may serve as a diagnostic marker for insulin-secreting lesions and a potential therapeutic target in insulinoma. It provides mechanistic insights that may inform future strategies for precision diagnostics and treatment of functional pancreatic neuroendocrine tumors.

Indexed as

Guanine Nucleotide Exchange FactorsInsulinInsulinomaInsulin SecretionPancreatic NeoplasmsAnimalsCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansInsulin-Secreting CellsMaleMiceOrganoidsXenograft Model Antitumor AssaysGuanine Nucleotide Exchange FactorsInsulinDOCK10InsulinomaInsulin SecretionPancreatic Neuroendocrine Tumor

Identifiers

PMID41389876
PMCPMC12973751

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

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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.