Evidence map›Paper›PMID 39627229›Full record

ArticleNature communications2024

Spint1 disruption in mouse pancreas leads to glucose intolerance and impaired insulin production involving HEPSIN/MAFA.

Hsin-Hsien Lin, I-Shing Yu, Ming-Shan Cheng, Tien-Jyun Chang, Hsin-Ying Lin, Yi-Cheng Chang, Chun-Jung Ko, Ping-Hung Chen, Shu-Wha Lin, Tai-Chung Huang and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

15 authors.

Hsin-Hsien LinDepartment of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
I-Shing YuLaboratory Animal Center, College of Medicine, National Taiwan University, Taipei, Taiwan.ORCID 0000-0002-2369-5816
Ming-Shan ChengDepartment of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Tien-Jyun ChangDepartment of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Hsin-Ying LinDepartment of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Yi-Cheng ChangGraduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei, Taiwan.ORCID 0000-0002-8077-5011
Chun-Jung KoGraduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan.ORCID 0000-0001-6565-7060
Ping-Hung ChenDepartment of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.ORCID 0000-0002-7156-0510
Shu-Wha LinLaboratory Animal Center, College of Medicine, National Taiwan University, Taipei, Taiwan.
Tai-Chung HuangDepartment of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.ORCID 0000-0002-1625-7295
Shin-Yi HuangDepartment of Pathology, National Taiwan University Hospital, Taipei, Taiwan.
Tzu-Yu ChenGraduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei, Taiwan.ORCID 0000-0003-1037-3882
Kai-Wen KanDepartment of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Hsiang-Po HuangGraduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei, Taiwan. hphuang691290@g.ntu.edu.tw.ORCID 0000-0002-3382-305X
Ming-Shyue LeeDepartment of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan. mslee2006@ntu.edu.tw.ORCID 0000-0002-8673-5088

Funding

National Health Research Institutes (NHRI) EX109-10725BI
6 · The paper itself

Abstract

SPINT1, a membrane-anchored serine protease inhibitor, regulates cascades of pericellular proteolysis while its tissue-specific functions remain incompletely characterized. In this study, we generate Spint1-lacZ knock-in mice and observe Spint1 expression in embryonic pancreatic epithelium. Pancreas-specific Spint1 disruption significantly diminishes islet size and mass, causing glucose intolerance and downregulation of MAFA and insulin. Mechanistically, the serine protease HEPSIN interacts with SPINT1 in β cells, and Hepsin silencing counteracts the downregulation of Mafa and Ins1 caused by Spint1 depletion. Furthermore, we demonstrate a potential interaction between HEPSIN and GLP1R in β cells. Spint1 silencing or Hepsin overexpression reduces GLP1R-related cyclic AMP levels and Mafa expression. Spint1-disrupted mice also exhibit a significant reduction in Exendin-4-induced insulin secretion. Moreover, SPINT1 expression increases in islets of prediabetic humans compared to non-prediabetic groups. The results unveil a role for SPINT1 in β cells, modulating glucose homeostasis and insulin production via HEPSIN/MAFA signaling.

Indexed as

Glucose IntoleranceInsulinInsulin-Secreting CellsSerine EndopeptidasesAnimalsFemaleGlucagon-Like Peptide-1 ReceptorGlucoseHumansInsulin SecretionMaf Transcription Factors, LargeMaleMiceMice, Inbred C57BLPancreasPrediabetic StateGlucagon-Like Peptide-1 ReceptorGlucosehepsinInsulinMaf Transcription Factors, LargeSerine Endopeptidases

Identifiers

PMID39627229
PMCPMC11615295

What Socratic holds

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LicenceCC BY-NC-ND
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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.