Evidence mapPaperPMID 42464935Full record

ArticleThe Journal of physiology2026

Pancreatic cancer cachexia promotes cardiac dysfunction through altered adrenergic signalling in the heart.

Parham Diba, Peter R Levasseur, Samuel D Newton, Khia Min Sabrina Koh, Paige C Arneson-Wissink, Xinxia Zhu, Peter Pham, Heike Mendez, Luke Whitcomb, Ariana Sattler and 4 more

Abstract read
In one paragraph

Article in The Journal of physiology, 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

14 authors.

Parham DibaMedical Scientist Training Program, Oregon Health and Science University, Portland, Oregon, USA.ORCID https://orcid.org/0000-0003-1014-510X
Peter R LevasseurDepartment of Radiation Medicine, Oregon Health and Science University, Portland, Oregon, USA.
Samuel D NewtonDepartment of Pediatrics, Oregon Health and Science University, Portland, Oregon, USA.ORCID https://orcid.org/0009-0002-3926-7709
Khia Min Sabrina KohDepartment of Chemical Physiology and Biochemistry, Oregon Health and Science University, Portland, Oregon, USA.
Paige C Arneson-WissinkDepartment of Radiation Medicine, Oregon Health and Science University, Portland, Oregon, USA.ORCID https://orcid.org/0000-0002-2706-9652
Xinxia ZhuDepartment of Radiation Medicine, Oregon Health and Science University, Portland, Oregon, USA.ORCID https://orcid.org/0009-0009-4041-1561
Peter PhamDepartment of Radiation Medicine, Oregon Health and Science University, Portland, Oregon, USA.
Heike MendezDepartment of Radiation Medicine, Oregon Health and Science University, Portland, Oregon, USA.
Luke WhitcombMedical Scientist Training Program, Oregon Health and Science University, Portland, Oregon, USA.
Ariana SattlerCancer Early Detection Advanced Research Center, Kight Cancer Institute, Oregon Health and Science University, Portland, Oregon, USA.
William R WoodwardDepartment of Chemical Physiology and Biochemistry, Oregon Health and Science University, Portland, Oregon, USA.
Beth A HabeckerDepartment of Chemical Physiology and Biochemistry, Oregon Health and Science University, Portland, Oregon, USA.ORCID https://orcid.org/0000-0002-4658-8730
Daniel L MarksEndevica Bio, Northbrook, Illinois, USA.ORCID https://orcid.org/0000-0003-2675-7047
Aaron J GrossbergDepartment of Radiation Medicine, Oregon Health and Science University, Portland, Oregon, USA.

Funding

Peripheral Sympathetic Dysfunction in Cardiac DiseaseR01HL146833 · OREGON HEALTH & SCIENCE UNIVERSITY · 2025 to 2025
$686k
Neurotrophins and post-infarct plasticity in cardiac sympathetic neuronsR01HL093056 · OREGON HEALTH & SCIENCE UNIVERSITY · 2025 to 2025
$655k
PQ6: Therapeutic approaches for autonomic and neuroendocrine dysfunction in cancer cachexiaR01CA264133 · OREGON HEALTH & SCIENCE UNIVERSITY · 2025 to 2025
$433k
Metabolic vulnerability due to dysregulated lipid metabolism in PDAC cachexiaR37CA280692 · OREGON HEALTH & SCIENCE UNIVERSITY · 2025 to 2025
$378k
National Cancer Institute of National Institute of Health K99CA286709National Heart, Lung, and Blood Institute of the National Institute of Health F30HL170476NCI NIH HHS R01 CA264133NCI NIH HHS R37 CA280692NHLBI NIH HHS R01 HL093056NHLBI NIH HHS R01 HL146833the Oregon Clinical and Translational Research Institute (OCTRI) TL1TR002371
6 · The paper itself

Abstract

Cancer cachexia is a metabolic syndrome commonly observed in patients with pancreatic ductal adenocarcinoma (PDAC), characterized by wasting of skeletal and cardiac muscle. This condition is associated with the neurohormonal stress response and activation of the sympathetic nervous system. However the impact of cachexia on cardiac adrenergic signalling remains poorly understood. Here we used a preclinical model of PDAC cachexia to investigate how sympathetic input to the heart is altered. We found desensitization of β1-adrenergic receptor (β1-AR) in the heart, along with evidence of increased adrenergic tone. Pharmacological blockade with the β1-selective antagonist metoprolol partially restored adrenergic responsiveness in PDAC mice, suggesting that elevated adrenergic drive contributes to β1-AR desensitization. The impaired β1-AR sensitivity blunted the chronotropic response to dobutamine and reduced inotropic reserve under adrenergic stress. Together these findings uncover disruption of cardiac adrenergic signalling in PDAC cachexia. KEY POINTS: Pancreatic cancer-associated cachexia promotes β1-adrenergic receptor desensitization in the heart. Pancreatic cancer-induced β1-adrenergic receptor desensitization is partly mediated by increased adrenergic transmission to the heart. β1-adrenergic receptor desensitization in mice with pancreatic cancer reduces contractile reserve under adrenergic stress.

Indexed as

CachexiaHeartPancreatic NeoplasmsReceptors, Adrenergic, beta-1Adrenergic beta-1 Receptor AntagonistsAnimalsMaleMetoprololMiceMice, Inbred C57BLMyocardiumSignal TransductionAdrenergic beta-1 Receptor AntagonistsMetoprololReceptors, Adrenergic, beta-1adrenergic signallingcachexiacardiac physiologydesensitizationheart ratepancreatic cancersympathetic nervous system

Identifiers

PMID42464935
PMCPMC13423009

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.