Evidence map›Paper›PMID 41528843›Full record

ArticleCell reports2026

PDX1 phosphorylation at S61 by mTORC1 links nutrient signaling to β cell function and metabolic disease.

Jialin Fan, Xin Zhang, Jinling Zhang, Tinghan Zhao, Stephen K Burley, X F Steven Zheng

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed, 6 pooled it
–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

53 citing papers in PubMed, 6 syntheses or guidelines pooled it.

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  16. Slower Progression Rates in Lower Limb-Onset ALS.Journal of clinical medicine · 2026
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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

6 authors.

Jialin FanRutgers Cancer Institute, Rutgers, the State University of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08901, USA; Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers, the State University of New Jersey, 675 Hoes Lane, Piscataway, NJ 08854, USA.
Xin ZhangRutgers Cancer Institute, Rutgers, the State University of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08901, USA; Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers, the State University of New Jersey, 675 Hoes Lane, Piscataway, NJ 08854, USA.
Jinling ZhangRutgers Cancer Institute, Rutgers, the State University of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08901, USA; Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers, the State University of New Jersey, 675 Hoes Lane, Piscataway, NJ 08854, USA.
Tinghan ZhaoRutgers Cancer Institute, Rutgers, the State University of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08901, USA; Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers, the State University of New Jersey, 675 Hoes Lane, Piscataway, NJ 08854, USA.
Stephen K BurleyRutgers Cancer Institute, Rutgers, the State University of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08901, USA; RCSB Protein Data Bank and Institute for Quantitative Biomedicine, Rutgers, the State University of New Jersey, 174 Frelinghuysen Road, Piscataway, NJ 08854, USA; Rutgers Artificial Intelligence and Data Science (RAD) Collaboratory, Rutgers, the State University of New Jersey, 174 Frelinghuysen Road, Piscataway, NJ 08854, USA; Department of Chemistry and Chemical Biology, Rutgers, the State University of New Jersey, 80 Bevier Road, Piscataway, NJ 08854, USA; RCSB Protein Data Bank and Institute for Quantitative Biomedicine, San Diego Supercomputer Center, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
X F Steven ZhengRutgers Cancer Institute, Rutgers, the State University of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08901, USA; Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers, the State University of New Jersey, 675 Hoes Lane, Piscataway, NJ 08854, USA. Electronic address: zhengst@cinj.rutgers.edu.

Funding

Metabolic Control and Anticancer MechanismR01CA260006 · NCI · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · PI STEVEN ZHENG · 2021 to 2026
$1.7M
Amino Acids-Rab1A Nutrient Signaling in the Regulation of Glucose HomeostasisR01DK124897 · NIDDK · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · PI ZHENG, STEVEN · 2020 to 2023
$1.5M
NCI NIH HHS R01 CA260006NIDDK NIH HHS R01 DK124897
6 · The paper itself

Abstract

PDX1 is a key transcription factor regulating insulin expression in response to glucose. Our previous work showed that PDX1 is also stimulated by amino acids (aa). Here, we demonstrate that PDX1 broadly mediates aa-regulated transcriptional programs in β cells, especially those controlling β cell proliferation and function. Mechanistically, mTORC1 phosphorylates PDX1 at serine 61 (S61), enhancing its protein stability and transcriptional activity. A certain monogenic diabetes mutation disrupts this phosphorylation and impairs PDX1 function. To investigate its physiological role, we generated mice carrying S61A and S61E mutations, mimicking unphosphorylated and phosphorylated states. S61 phosphorylation promoted insulin expression and β cell proliferation, leading to Western diet-induced hyperinsulinemia, obesity, and hepatic steatosis. These findings reveal the central role of aa-mTORC1-PDX1 signaling in coordinating β cell proliferation and function under both physiological and pathological conditions.

Indexed as

Homeodomain ProteinsInsulin-Secreting CellsMechanistic Target of Rapamycin Complex 1Metabolic DiseasesNutrientsTrans-ActivatorsAmino AcidsAnimalsCell ProliferationHumansInsulinMiceMice, Inbred C57BLPhosphorylationSignal TransductionAmino AcidsHomeodomain ProteinsInsulinMechanistic Target of Rapamycin Complex 1pancreatic and duodenal homeobox 1 proteinTrans-Activatorsamino acidsCP: metabolismCP: molecular biologydiabetesglucosehyperinsulinemiainsulinliver steatosisMODYmTORnutrientsobesitypdx1β cell

Identifiers

PMID41528843
PMCPMC12949489

What OpenQuestion holds

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Registered trials

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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.