---
title: "INSR–BECN1–KIAA0825 complex prevents hepatocytic insulin receptor secretion and guards against mon"
id: "biorxiv-17-an-insr-becn1-kiaa0825-complex-prevents-hepatocytic-insulin-receptor-secretion"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-17-an-insr-becn1-kiaa0825-complex-prevents-hepatocytic-insulin-receptor-secretion"
content_type: "clinical_feed_article"
specialty: "Endocrinology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.09.13.751259v1?rss=1"
published_at: "2026-09-17T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# INSR–BECN1–KIAA0825 complex prevents hepatocytic insulin receptor secretion and guards against mon
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-17-an-insr-becn1-kiaa0825-complex-prevents-hepatocytic-insulin-receptor-secretion
- **Specialty:** [Endocrinology](https://medichelpline.com/clinical-feed/endocrinology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.09.13.751259v1?rss=1)
- **Published At:** 2026-09-17T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- Researchers identified a protein complex of **INSR** (insulin receptor), **BECN1**, and **KIAA0825** that regulates insulin receptor sorting and presentation in hepatocytes. - Disruption of any component — loss of hepatic **BECN1** or **KIAA0825**, or expression of monogenic diabetes-causing **INSR** mutations — breaks the complex and reroutes INSR into **extracellular vesicles** for secretion from hepatocytes. - Secretion of INSR via extracellular vesicles reduces hepatocytic INSR cell-surface presentation, impairing hepatic insulin signaling and sensitivity. - Consequences of disrupted complex and INSR misrouting include defective hepatic **glycogen storage** and reduced exercise capacity, linking receptor trafficking to systemic metabolic outcomes. - The data reveal a previously unrecognized, non-canonical, non-degradative role for **BECN1** in receptor trafficking rather than autophagic degradation. - **KIAA0825**, previously a diabetic-risk gene of unknown function, is implicated as a regulator of INSR transport and membrane presentation in the liver. - Findings define a cellular fate for pathogenic **INSR** mutants in monogenic diabetes: mutant receptors are mis-sorted and secreted rather than retained or degraded, providing a mechanistic explanation for impaired receptor function. - These results highlight new molecular regulators and mechanisms that govern INSR sorting, trafficking, and signaling in hepatocytes and suggest potential targets for further study in monogenic and possibly other forms of insulin resistance. - The work is presented as a preprint and has not been peer-reviewed; details on experimental approaches and quantitative data were not reported in the abstract and should be consulted in the full manuscript for confirmation.
## Clinical Analysis & Structured Key Points
An INSR-BECN1-KIAA0825 complex prevents hepatocytic insulin receptor secretion via extracellular vesicles against monogenic diabetes | bioRxiv Skip to main content New Results An INSR-BECN1-KIAA0825 complex prevents hepatocytic insulin receptor secretion via extracellular vesicles against monogenic diabetes Kenta Kuramoto , Min Chen , Congcong He doi: https://doi.org/10.64898/2026.09.13.751259 Kenta Kuramoto Northwestern University Find this author on Google Scholar Find this author on PubMed Search for this author on this site Min Chen Northwestern University Find this author on Google Scholar Find this author on PubMed Search for this author on this site Congcong He Northwestern University Find this author on Google Scholar Find this author on PubMed Search for this author on this site For correspondence: congcong.he{at}northwestern.edu Abstract Info/History Metrics Preview PDF Abstract Monogenic diabetes from insulin receptor (INSR) mutations is a rare genetic disorder causing early-onset, profound insulin resistance. However, the pathogenic mechanisms by which INSR mutations disrupt receptor trafficking, cell-surface stability, and signaling are unresolved, and consequently, current treatment remains largely symptomatic and prognosis is not optimal. Here we discover that INSR, the autophagy protein BECN1, and KIAA0825, encoded by a diabetic-risk gene of previously unknown function, form a complex to regulate INSR transport, membrane presentation, and functionality in hepatocytes. Loss of hepatic BECN1 or KIAA0825, or expression of monogenic diabetes-causing mutations in INSR, disrupts the INSR-BECN1-KIAA0825 complex and mis-routes INSR to extracellular vesicles for secretion from hepatocytes, leading to impaired hepatocytic INSR cell-surface presentation and defects in hepatic insulin sensitivity, glycogen storage and exercise capacity. These findings identify new regulators and mechanisms governing INSR sorting, trafficking and signaling, uncover a non-canonical, non-degradative role for BECN1, and reveal the cellular fate of pathogenic INSR mutants underlying monogenic diabetes. Competing Interest Statement The authors have declared no competing interest. Funder Information Declared NIH Common Fund, https://ror.org/001d55x84 , R01 DK113170 , R01 DK123447 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license . Back to top Previous Next Posted September 17, 2026. Download PDF Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following An INSR-BECN1-KIAA0825 complex prevents hepatocytic insulin receptor secretion via extracellular vesicles against monogenic diabetes Message Subject (Your Name) has forwarded a page to you from bioRxiv Message Body (Your Name) thought you would like to see this page from the bioRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share An INSR-BECN1-KIAA0825 complex prevents hepatocytic insulin receptor secretion via extracellular vesicles against monogenic diabetes Kenta Kuramoto , Min Chen , Congcong He bioRxiv 2026.09.13.751259; doi: https://doi.org/10.64898/2026.09.13.751259 Share This Article: Copy Citation Tools An INSR-BECN1-KIAA0825 complex prevents hepatocytic insulin receptor secretion via extracellular vesicles against monogenic diabetes Kenta Kuramoto , Min Chen , Congcong He bioRxiv 2026.09.13.751259; doi: https://doi.org/10.64898/2026.09.13.751259 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Areas All Articles Animal Behavior and Cognition (8003) Biochemistry (18709) Bioengineering (14841) Bioinformatics (44370) Biophysics (22563) Cancer Biology (19685) Cell Biology (26852) Clinical Trials (138) Developmental Biology (13945) Ecology (20975) Epidemiology (2067) Evolutionary Biology (25417) Genetics (16151) Genomics (23481) Immunology (18683) Microbiology (42423) Molecular Biology (18027) Neuroscience (93361) Paleontology (699) Pathology (2977) Pharmacology and Toxicology (5086) Physiology (8105) Plant Biology (15971) Scientific Communication and Education (2095) Synthetic Biology (4551) Systems Biology (10221) Zoology (2384)
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