---
title: "Endogenous insulin links pancreatic ductal adenocarcinoma growth with host systemic metabolism"
id: "biorxiv-21-endogenous-insulin-mediates-dynamic-coordination-between-pancreatic-cancer-and"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-21-endogenous-insulin-mediates-dynamic-coordination-between-pancreatic-cancer-and"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.08.26.745597v1?rss=1"
published_at: "2026-08-27T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Endogenous insulin links pancreatic ductal adenocarcinoma growth with host systemic metabolism
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-21-endogenous-insulin-mediates-dynamic-coordination-between-pancreatic-cancer-and
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.08.26.745597v1?rss=1)
- **Published At:** 2026-08-27T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- This preprint examined how **endogenous insulin** coordinates metabolic interactions between pancreatic ductal adenocarcinoma (**PDAC**) and the host using an orthotopic transplantation model of patient-derived organoids in mice. - Mice were fed a **high-fat diet (HFD)** that induces hyperinsulinemia to test diet-driven effects on tumor growth and host physiology. - Tumor insulin concentrations were higher than circulating insulin levels, indicating localized insulin accumulation or production within tumors. - Genetically lowering insulin levels reduced PDAC growth; this effect was most pronounced in **HFD-fed mature male mice**. - The presence of pancreatic tumors altered host systemic metabolism: tumors increased glucose clearance and blunted HFD-driven increases in circulating insulin, body weight, and fat mass. - In mice fed normal chow (not HFD), tumor growth correlated with falling circulating insulin as well as losses of fat and muscle mass, linking tumor progression to features of cancer-associated cachexia. - The data support a complex, dynamic, insulin-centered interplay between PDAC and host metabolism that contributes to cancer-associated metabolic dysfunction. - The authors disclose a competing interest: Christoph H. Borchers holds industry advisory and executive proteomics roles. - The study is reported as a bioRxiv preprint (posted August 27, 2026); details such as exact genetic manipulations, quantitative values, sample sizes, and full methods are not reported in the source abstract.
## Clinical Analysis & Structured Key Points
Endogenous insulin mediates dynamic coordination between pancreatic cancer and systemic metabolism | bioRxiv Skip to main content New Results Endogenous insulin mediates dynamic coordination between pancreatic cancer and systemic metabolism Jeffrey S.H Lin , Aman A Mohammed , Keeley G Hewton , Jingqiang Wang , Tiffany Z.Y Chen , Ivy S.Y Guo , Riley S.H Lam , Marcelo Ferraz Reinaldo , Vincent R Richard , David F Schaeffer , Daniel J Renouf , Christoph H Borchers , Seth J Parker , Josef M Penninger , James D Johnson , Janel L Kopp doi: https://doi.org/10.64898/2026.08.26.745597 Jeffrey S.H Lin 1 University of British Columbia; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Aman A Mohammed 1 University of British Columbia; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Keeley G Hewton 1 University of British Columbia; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Jingqiang Wang 1 University of British Columbia; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Tiffany Z.Y Chen 1 University of British Columbia; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Ivy S.Y Guo 1 University of British Columbia; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Riley S.H Lam 1 University of British Columbia; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Marcelo Ferraz Reinaldo 1 University of British Columbia; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Vincent R Richard 2 McGill University Find this author on Google Scholar Find this author on PubMed Search for this author on this site David F Schaeffer 1 University of British Columbia; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Daniel J Renouf 1 University of British Columbia; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Christoph H Borchers 2 McGill University Find this author on Google Scholar Find this author on PubMed Search for this author on this site Seth J Parker 1 University of British Columbia; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Josef M Penninger 1 University of British Columbia; Find this author on Google Scholar Find this author on PubMed Search for this author on this site James D Johnson 1 University of British Columbia; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Janel L Kopp 1 University of British Columbia; Find this author on Google Scholar Find this author on PubMed Search for this author on this site For correspondence: janel.kopp{at}ubc.ca Abstract Info/History Metrics Supplementary material Preview PDF Abstract Pancreatic ductal adenocarcinoma (PDAC) is commonly associated with obesity, diabetes, and cachexia. The pancreatic anabolic hormone, insulin, is implicated in each of these metabolic diseases, but how insulin levels affect tumor growth and relevant host physiological factors, was unclear. To address this, we transplanted orthotopic PDAC patient-derived organoids into mice consuming a hyperinsulinemia-inducing high-fat diet (HFD). We found that insulin concentrations were higher in tumors compared to circulation. Genetically reducing insulin levels reduced PDAC growth, particularly in HFD-fed mature male mice. In turn, we found the presence of pancreatic tumors increased glucose clearance and limited the expected dietary-induced gains in insulin, weight and fat mass. Interestingly, tumor growth in normal-chow-fed mice, but not HFD-fed mice, was associated with declining circulating insulin levels, as well as declines in fat and muscle mass. Together, these data provide new insights into the complex, insulin-centred interplay between PDAC and the hosts systemic metabolism that underlie cancer-associated metabolic dysfunction. Competing Interest Statement Christoph H. Borchers is the Scientific Advisor of MRM Proteomics Inc. and the VP of Proteomics at Molecular You. 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-NC-ND 4.0 International license . Back to top Previous Next Posted August 27, 2026. Download PDF Supplementary Material 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. 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Share Endogenous insulin mediates dynamic coordination between pancreatic cancer and systemic metabolism Jeffrey S.H Lin , Aman A Mohammed , Keeley G Hewton , Jingqiang Wang , Tiffany Z.Y Chen , Ivy S.Y Guo , Riley S.H Lam , Marcelo Ferraz Reinaldo , Vincent R Richard , David F Schaeffer , Daniel J Renouf , Christoph H Borchers , Seth J Parker , Josef M Penninger , James D Johnson , Janel L Kopp bioRxiv 2026.08.26.745597; doi: https://doi.org/10.64898/2026.08.26.745597 Share This Article: Copy Citation Tools Endogenous insulin mediates dynamic coordination between pancreatic cancer and systemic metabolism Jeffrey S.H Lin , Aman A Mohammed , Keeley G Hewton , Jingqiang Wang , Tiffany Z.Y Chen , Ivy S.Y Guo , Riley S.H Lam , Marcelo Ferraz Reinaldo , Vincent R Richard , David F Schaeffer , Daniel J Renouf , Christoph H Borchers , Seth J Parker , Josef M Penninger , James D Johnson , Janel L Kopp bioRxiv 2026.08.26.745597; doi: https://doi.org/10.64898/2026.08.26.745597 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 (7933) Biochemistry (18545) Bioengineering (14704) Bioinformatics (43933) Biophysics (22349) Cancer Biology (19476) Cell Biology (26648) Clinical Trials (138) Developmental Biology (13849) Ecology (20787) Epidemiology (2067) Evolutionary Biology (25206) Genetics (16047) Genomics (23313) Immunology (18506) Microbiology (42050) Molecular Biology (17868) Neuroscience (92446) Paleontology (691) Pathology (2953) Pharmacology and Toxicology (5045) Physiology (8025) Plant Biology (15818) Scientific Communication and Education (2090) Synthetic Biology (4519) Systems Biology (10147) Zoology (2367)
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