Evidence mapPaperPMID 39899446Full record

ArticleDiabetes2025

Atf4 Protects Islet β-Cell Identity and Function Under Acute Glucose-Induced Stress but Promotes β-Cell Failure in the Presence of Free Fatty Acid.

Mahircan Yagan, Sadia Najam, Ruiying Hu, Yu Wang, Mathew T Dickerson, Prasanna K Dadi, Yanwen Xu, Alan J Simmons, Roland Stein, Christopher M Adams and 4 more

Abstract read
In one paragraph

Article in Diabetes, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Insulin Resistance and Inflammation.International journal of molecular sciences · 2026
    Review
  5. Review
  6. Article
  7. Altered Expression of theNutrients · 2025
    Article
  8. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Mahircan YaganDepartment of Cell and Developmental Biology and Center for Stem Cell Biology, Vanderbilt University School of Medicine, Nashville, TN.
Sadia NajamDepartment of Cell and Developmental Biology and Center for Stem Cell Biology, Vanderbilt University School of Medicine, Nashville, TN.
Ruiying HuDepartment of Cell and Developmental Biology and Center for Stem Cell Biology, Vanderbilt University School of Medicine, Nashville, TN.
Yu WangDepartment of Biostatistics and Center for Quantitative Sciences, Vanderbilt Medical Center, Nashville, TN.
Mathew T DickersonDepartment of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN.
Prasanna K DadiDepartment of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN.
Yanwen XuDepartment of Cell and Developmental Biology and Center for Stem Cell Biology, Vanderbilt University School of Medicine, Nashville, TN.
Alan J SimmonsDepartment of Cell and Developmental Biology and Center for Stem Cell Biology, Vanderbilt University School of Medicine, Nashville, TN.
Roland SteinDepartment of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN.ORCID 0000-0001-9192-8661
Christopher M AdamsDivision of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, Rochester, MN.
David A JacobsonDepartment of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN.
Ken S LauDepartment of Cell and Developmental Biology and Center for Stem Cell Biology, Vanderbilt University School of Medicine, Nashville, TN.
Qi LiuDepartment of Biostatistics and Center for Quantitative Sciences, Vanderbilt Medical Center, Nashville, TN.
Guoqiang GuDepartment of Cell and Developmental Biology and Center for Stem Cell Biology, Vanderbilt University School of Medicine, Nashville, TN.ORCID 0000-0003-0772-9139

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Ben Ho Park · 1995 to 2026
$172.8M
Translational Analysis CoreP30DK058404 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 2002 to 2026
$29.9M
Vanderbilt Diabetes Research CenterP30DK020593 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI ALVIN C POWERS · 2012 to 2026
$29.3M
Shop Module CoreP30EY008126 · NEI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI David J. Calkins · 1989 to 2026
$19.6M
Vanderbilt Mouse Metabolic Physiology CenterU24DK059637 · NIDDK · VANDERBILT UNIVERSITY · PI WASSERMAN, DAVID H · 2001 to 2015
$14.9M
Shaping the Microenvironment by DPEP1 Facilitates Adenoma ProgressionU54CA274367 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Bhuminder Singh · 2022 to 2026
$9.7M
Tuft cell heterogeneity in function, lineage, and structure in ileal inflammatory diseaseR01DK103831 · NIDDK · VANDERBILT UNIVERSITY · PI LAU, KEN S · 2016 to 2024
$4.4M
The DNA methylome-based regulation of functional beta-cell massR01DK125696 · NIDDK · VANDERBILT UNIVERSITY · PI Guoqiang Gu · 2020 to 2026
$3.4M
Molecular Mechanisms Regulating Pancreatic Delta Cell Function and DysfunctionR01DK129340 · NIDDK · VANDERBILT UNIVERSITY · PI David Aaron Jacobson · 2022 to 2026
$2.3M
Secretagogue and Gi/o-GPCR signaling through the islet Na+/K+-ATPase in health and diabetesR01DK136768 · NIDDK · VANDERBILT UNIVERSITY · PI David Aaron Jacobson · 2023 to 2026
$2.0M
Regulating stress response to promote postnatal beta-cell function and survivalR01DK128710 · NIDDK · VANDERBILT UNIVERSITY · PI GU, GUOQIANG · 2021 to 2024
$1.9M
American Cancer Society CA095103Division of Diabetes, Endocrinology, and Metabolic Diseases DK103831NCI NIH HHS P30 CA068485NCI NIH HHS U54 CA274367NEI NIH HHS P30 EY008126NIDDK NIH HHS P30 DK020593NIDDK NIH HHS P30 DK058404NIDDK NIH HHS R01 DK103831NIDDK NIH HHS R01 DK125696NIDDK NIH HHS R01 DK128710NIDDK NIH HHS R01 DK129340NIDDK NIH HHS R01 DK136768NIDDK NIH HHS U24 DK059637
6 · The paper itself

Abstract

Glucolipotoxicity, caused by combined hyperglycemia and hyperlipidemia, results in β-cell failure and type 2 diabetes via cellular stress-related mechanisms. Activating transcription factor 4 (Atf4) is an essential effector of stress response. We show here that Atf4 expression in β-cells is minimally required for glucose homeostasis in juvenile and adolescent mice but it is needed for β-cell function during aging and under obesity-related metabolic stress. Henceforth, Atf4-deficient β-cells older than 2 months after birth display compromised secretory function under acute hyperglycemia. In contrast, they are resistant to acute free fatty acid-induced dysfunction and reduced production of several factors essential for β-cell identity. Atf4-deficient β-cells downregulate genes involved in protein translation. They also upregulate several lipid metabolism or signaling genes, likely contributing to their resistance to free fatty acid-induced dysfunction. These results suggest that Atf4 activation is required for β-cell identity and function under high glucose. But Atf4 activation paradoxically induces β-cell failure in high levels of free fatty acids. Different transcriptional targets of Atf4 could be manipulated to protect β-cells from metabolic stress-induced failure. ARTICLE HIGHLIGHTS:

Indexed as

Activating Transcription Factor 4Fatty Acids, NonesterifiedGlucoseInsulin-Secreting CellsStress, PhysiologicalAnimalsHyperglycemiaLipid MetabolismMaleMiceMice, Inbred C57BLMice, KnockoutActivating Transcription Factor 4Atf4 protein, mouseFatty Acids, NonesterifiedGlucose

Identifiers

PMID39899446
PMCPMC12015139

What Socratic holds

Textmetadata
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.