Evidence mapPaperPMID 41022721Full record

ArticleNature communications2025

Prolonged glucagon exposure rewires lipid oxidation and drives diabetic kidney disease progression.

Xingfeng Liu, Jingwen Chen, Shengying Gu, Yibing Chen, Ruiping Zhang, Qingce Zang, Ting Li, Hanwen Li, Dejin Lu, Shaocong Hou and 13 more

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 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
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

23 authors.

Xingfeng Liu *State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.ORCID http://orcid.org/0000-0002-7518-5797
Jingwen Chen *State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Shengying Gu *State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Yibing ChenState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Ruiping ZhangState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.ORCID http://orcid.org/0000-0001-6482-9991
Qingce ZangState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.ORCID http://orcid.org/0000-0001-8220-1508
Ting LiState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Hanwen LiState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Dejin LuState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Shaocong HouState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.ORCID http://orcid.org/0000-0003-0442-8138
Lijuan KongState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.ORCID http://orcid.org/0009-0005-7194-1443
Qian JiangState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.ORCID http://orcid.org/0000-0002-3969-9141
Caiyi XingState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Wenjia FanState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Yanjun WanState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Jiaqi ZhangState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Linyuan ZhuState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Chunxiao MaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Qijin ZhaoState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.ORCID http://orcid.org/0000-0002-1216-1640
Hai YanREMD Biotherapeutics Inc., Camarillo, CA, USA.
Zeper AblizState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.ORCID http://orcid.org/0000-0002-4876-2392
Bing CuiState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. cuibing@imm.ac.cn.ORCID http://orcid.org/0000-0001-8374-7801
Pingping LiState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. lipp@imm.ac.cn.ORCID http://orcid.org/0000-0003-0679-270X

Funding

National Natural Science Foundation of China (National Science Foundation of China) 8252500819
6 · The paper itself

Abstract

Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease. Tubular abnormalities may precede glomerular pathology and indicate functional progression of DKD. Here, we find glucagon injection exacerbates lipid accumulation and renal injury, in addition to causing morphological changes in proximal tubules, podocytes, and mitochondria in the early phase of DKD in mice. However, the specific knockdown or knockout of Gcgr in renal tubular epithelial cells almost completely halts DKD development. In contrast to the effect of short-term glucagon stimulation, long-term glucagon exposure leads to the reversal of glucagon action (glucagon reversal) in proximal tubular epithelial cells (PTECs), which is characterized by reduced energy production and an increase in lipogenesis through Gcgr-PKA-Creb-mTORC1 pathway. Accordingly, anti-GCGR antibody treatment strongly blocks the pathogenesis of DKD induced by both type 2 and type 1 diabetes. Thus, our results highlight a previously unrecognized role of glucagon/Gcgr signaling in PTEC lipogenesis and DKD.

Indexed as

Diabetic NephropathiesGlucagonLipid MetabolismAnimalsCyclic AMP Response Element-Binding ProteinDiabetes Mellitus, ExperimentalDisease ProgressionEpithelial CellsHumansKidney Tubules, ProximalLipogenesisMaleMechanistic Target of Rapamycin Complex 1MiceMice, Inbred C57BLMice, KnockoutCyclic AMP Response Element-Binding ProteinGlucagonMechanistic Target of Rapamycin Complex 1Receptors, Glucagon

Identifiers

PMID41022721
PMCPMC12479795

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.