Evidence map›Paper›PMID 40075066›Full record

ArticleNature communications2025

Blockade of glucagon receptor induces α-cell hypersecretion by hyperaminoacidemia in mice.

Jianxin Jia, Xuanxuan Bai, Qi Kang, Fuquan Jiang, F Susan Wong, Quanwen Jin, Mingyu Li

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

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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

7 authors.

Jianxin JiaState Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences and School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, China.ORCID http://orcid.org/0009-0005-8722-641X
Xuanxuan BaiState Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences and School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, China.
Qi KangState Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences and School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, China.
Fuquan JiangFujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen, China.
F Susan WongDivision of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK.
Quanwen JinState Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences and School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, China. jinquanwen@xmu.edu.cn.ORCID http://orcid.org/0000-0001-6146-6910
Mingyu LiState Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences and School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, China. limingyu@xmu.edu.cn.ORCID http://orcid.org/0000-0003-1217-2929

Funding

Natural Science Foundation of Fujian Province (Fujian Provincial Natural Science Foundation) 2023I0002
6 · The paper itself

Abstract

Blockade of the glucagon receptor (GCGR) has been shown to improve glycemic control. However, this therapeutic approach also brings side effects, such as α-cell hyperplasia and hyperglucagonemia, and the mechanisms underlying these side effects remain elusive. Here, we conduct single-cell transcriptomic sequencing of islets from male GCGR knockout (GCGR-KO) mice. Our analysis confirms the elevated expression of Gcg in GCGR-KO mice, along with enhanced glucagon secretion at single-cell level. Notably, Vgf (nerve growth factor inducible) is specifically upregulated in α cells of GCGR-KO mice. Inhibition of VGF impairs the formation of glucagon immature secretory granules and compromises glucagon maturation, lead to reduced α-cell hypersecretion of glucagon. We further demonstrate that activation of both mTOR-STAT3 and ERK-CREB pathways, induced by elevated circulation amino acids, is responsible for upregulation of Vgf and Gcg expression following glucagon receptor blockade. Thus, our findings elucidate parts of the molecular mechanism underlying hyperglucagonemia in GCGR blockade.

Indexed as

Amino AcidsGlucagonGlucagon-Secreting CellsReceptors, GlucagonAnimalsCyclic AMP Response Element-Binding ProteinMaleMiceMice, Inbred C57BLMice, KnockoutSignal TransductionSingle-Cell AnalysisSTAT3 Transcription FactorTOR Serine-Threonine KinasesUp-RegulationAmino AcidsCyclic AMP Response Element-Binding ProteinGlucagonmTOR protein, mouseReceptors, GlucagonStat3 protein, mouseSTAT3 Transcription FactorTOR Serine-Threonine Kinases

Identifiers

PMID40075066
PMCPMC11903786

What OpenQuestion 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 OpenQuestion graph.