Evidence map›Paper›PMID 41518733›Full record

ArticleBiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie2026

Characterizing ghrelin's role in dysregulating GLP-1-mediated function and promoting the development of alcohol-associated liver disease.

Sundararajan Mahalingam, Ramesh Bellamkonda, Kusum K Kharbanda, Ojeshvi Ethiraj, Nagasundaram Nagarajan, Chittibabu Guda, Kanika Sharma, Micah B Schott, Carol A Casey, Lorenzo Leggio and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

11 authors.

Sundararajan MahalingamResearch Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Ramesh BellamkondaResearch Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Kusum K KharbandaResearch Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA; Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
Ojeshvi EthirajDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Nagasundaram NagarajanDepartment of Genetics, Cell Biology & Anatomy, University of Nebraska Medical Center, Omaha, NE, USA.
Chittibabu GudaDepartment of Genetics, Cell Biology & Anatomy, University of Nebraska Medical Center, Omaha, NE, USA.
Kanika SharmaMass Spectrometry Core, University of Nebraska Medical Center, Omaha, NE, USA.
Micah B SchottDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Carol A CaseyResearch Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA; Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
Lorenzo LeggioClinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse, Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism, Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore and Bethesda, MD, USA; Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences, Brown University, Providence, RI, USA; Division of Addiction Medicine, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA; Department of Neuroscience, Georgetown University Medical Center, Washington DC, USA.
Karuna RasineniResearch Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA; Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA. Electronic address: Karuna.rasineni@unmc.edu.

Funding

UNMC/EPPLEY CANCER CENTER SUPPORT GRANTP30CA036727 · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 1985 to 2025
$11.0M
The Role of TP-R on Alcohol-Induced Multi-Organ Damage: Liver and HeartP50AA030407 · NIAAA · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2023 to 2025
$4.7M
Nebraska Research Network in Functional GenomicsP20GM103427 · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2025 to 2025
$3.9M
Role of alcohol-induced ghrelin in modulating organ crosstalk to promote the development of fatty liver diseaseR01AA028504 · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2025 to 2025
$339k
BLRD VA I01 BX006064NCI NIH HHS P30 CA036727NIAAA NIH HHS P50 AA030407NIAAA NIH HHS R01 AA026723NIAAA NIH HHS R01 AA028504NIGMS NIH HHS P20 GM103427
6 · The paper itself

Abstract

This study investigated the complex interplay between two gut hormones, glucagon-like peptide-1 (GLP-1) and ghrelin and their role in the development of alcohol-associated liver disease (ALD). Previous studies conducted in our laboratory and others have shown that chronic alcohol exposure leads to increased serum ghrelin and GLP-1 levels. Paradoxically, despite increased GLP-1, insulin resistance and disrupted hepatic lipid metabolism was noted in chronic ethanol fed animals. These results suggested impaired GLP-1-mediated protective function in the presence of high ghrelin. Our recent studies also revealed that growth hormone secretagogue receptor (GHSR, which is the ghrelin receptor) knockout (GHSR-KO) rats fed ethanol were more insulin sensitive and were resistant to develop ALD despite reduced serum GLP-1 compared to ethanol-fed wildtypes. Based on these considerations, we hypothesized that alcohol-induced increases in ghrelin-GHSR interaction impairs GLP-1-mediated functions. We employed both in vivo and in vitro approaches, including chronic ethanol feeding of wild-type and GHSR-KO rats, ghrelin administration to chow-fed rats, GSHR and GLP-1 receptor (GLP-1R)-transfected hepatocytes, murine enteroendocrine GLUTag and HEK293T cells utilizing several techniques to test our hypothesis. Chronic ethanol feeding in wildtype rats increased GLP-1 and GLP-1R levels, while ethanol-fed GHSR-KO rats did not show this increase. Ghrelin promoted GHSR and GLP-1R interaction/dimerization, thereby reducing GLP-1 effects. Furthermore, in-silico molecular docking analysis identified specific amino acid residues in the transmembrane regions of both receptors that are predicted to mediate this interaction. Alcohol-induced increases in ghrelin modulate GLP-1-mediated functions through GHSR-GLP-1R interactions. Targeting this interaction could offer a potential therapeutic strategy for ALD.

Indexed as

GhrelinGlucagon-Like Peptide 1Liver Diseases, AlcoholicAnimalsEthanolGlucagon-Like Peptide-1 ReceptorHepatocytesHumansLiverMaleMiceRatsReceptors, GhrelinEthanolGhrelinGlucagon-Like Peptide 1Glucagon-Like Peptide-1 ReceptorReceptors, GhrelinAlcohol-associated liver diseaseGhrelinGhrelin receptor (GHSR) Glucagon-like peptide-1G-protein coupled receptorGut hormonesReceptor-receptor interactions

Identifiers

PMID41518733
PMCPMC12906898

What Socratic holds

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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.