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Updated: Jan 8, 2026

Studying the Hypothalamic Insulin Signal to Peripheral Glucose Intolerance with a Continuous Drug Infusion System into the Mouse Brain
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DOCK10 Regulates Insulin Hypersecretion in Insulinoma and Serves as a Diagnostic and Therapeutic Target

Hiromune Katsuda1, Go Ito2, Franziska Kimmig3

  • 1Department of Gastroenterology and Hepatology, Institute of Science Tokyo, Tokyo, Japan.

Cellular and Molecular Gastroenterology and Hepatology
|December 13, 2025
PubMed
Abstract

Insights

Researchers identified dedicator of cytokinesis 10 (DOCK10) as a key regulator of insulin secretion in insulinomas. Targeting the DOCK10-Cdc42 pathway may offer new diagnostic and therapeutic strategies for these rare pancreatic tumors.

Area of Science:

  • Endocrinology
  • Oncology
  • Molecular Biology

Background:

  • Insulinomas, rare pancreatic neuroendocrine neoplasms (pan-NENs), cause inappropriate insulin secretion, posing diagnostic and therapeutic challenges.
  • Current diagnostic tools and treatments for insulinomas are limited, indicating a critical need for novel approaches.

Purpose of the Study:

  • To elucidate the molecular mechanisms driving insulin hypersecretion in insulinomas.
  • To identify potential diagnostic markers and therapeutic targets for insulinoma.

Main Methods:

  • Established a biobank of human insulinoma specimens and organoids.
  • Conducted comprehensive transcriptomic analyses (bulk RNA-seq, scRNA-seq, qPCR, IHC).
  • Performed functional validation using cell lines, xenograft models, and patient-derived organoids.

Main Results:

  • Identified dedicator of cytokinesis 10 (DOCK10) as significantly overexpressed in insulin-secreting insulinoma components.
  • DOCK10 knockdown reduced glucose-stimulated insulin secretion in mouse cells and human organoids.
  • Inhibition of the DOCK10-Cdc42 pathway with ML141 decreased insulin hypersecretion and improved survival in a mouse model.

Conclusions:

  • The DOCK10-Cdc42 axis plays a crucial role in regulating insulin secretion in insulinoma.
  • DOCK10 shows potential as a diagnostic marker for insulin-secreting lesions.
  • DOCK10 represents a promising therapeutic target for insulinoma treatment.
Keywords:
DOCK10Insulin SecretionInsulinomaPancreatic Neuroendocrine Tumor

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