Evidence map›Paper›PMID 35954309›Full record

ArticleCells2022

The Protective Action of Metformin against Pro-Inflammatory Cytokine-Induced Human Islet Cell Damage and the Mechanisms Involved.

Laura Giusti, Marta Tesi, Federica Ciregia, Lorella Marselli, Lorenzo Zallocco, Mara Suleiman, Carmela De Luca, Silvia Del Guerra, Mariachiara Zuccarini, Marco Trerotola and 6 more

Registry-linked trialOpen access · goldFull text read
In one paragraph

Article in Cells, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05572060 (Effect of Metformin Use on Mortality in Diabetic and Non Diabetic Patients With Sepsis and Septic Shock.), which is not on this map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
5.4field-weighted citation impact, top 3% of its field
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.

NCT05572060 naunknown statusnot on this map

Effect of Metformin Use on Mortality in Diabetic and Non Diabetic Patients With Sepsis and Septic Shock.

TypeinterventionalSponsorAssiut UniversityRan2022 to 2025Enrolled75ConditionsSeptic ShockArmsMetformin, standardized protocol
3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 25 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Islet Tissue Macrophages in Immunity Homeostasis and Type 1 Diabetes.Clinical reviews in allergy & immunology · 2025
    Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Review
  14. Placental Mitochondrial Function and Dysfunction in Preeclampsia.International journal of molecular sciences · 2023
    Review
  15. 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

16 authors at 4 institutions in 2 countries.

Laura GiustiSchool of Pharmacy, University of Camerino, 62032 Camerino, Italy.ORCID 0000-0001-7366-1932
Marta TesiDepartment of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy.
Federica CiregiaDepartment of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy.
Lorella MarselliDepartment of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy.ORCID 0000-0002-6698-2962
Lorenzo ZalloccoDepartment of Pharmacy, University of Pisa, 56126 Pisa, Italy.ORCID 0000-0001-6385-4116
Mara SuleimanDepartment of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy.
Carmela De LucaDepartment of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy.
Silvia Del GuerraDepartment of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy.
Mariachiara ZuccariniCenter for Advanced Studies and Technologies (CAST), University of Chieti-Pescara, 66100 Chieti, Italy.
Marco TrerotolaCenter for Advanced Studies and Technologies (CAST), University of Chieti-Pescara, 66100 Chieti, Italy.ORCID 0000-0003-1855-7002
Decio L EizirikULB Center for Diabetes Research, Université Libre de Bruxelles, 1070 Brussels, Belgium.
Miriam CnopULB Center for Diabetes Research, Université Libre de Bruxelles, 1070 Brussels, Belgium.
Maria R MazzoniDepartment of Pharmacy, University of Pisa, 56126 Pisa, Italy.
Piero MarchettiDepartment of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy.
Antonio LucacchiniDepartment of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy.ORCID 0000-0002-0917-4491
Maurizio RonciCenter for Advanced Studies and Technologies (CAST), University of Chieti-Pescara, 66100 Chieti, Italy.ORCID 0000-0002-0797-6087
University of Pisa · ITUniversity of Chieti-Pescara · ITUniversité Libre de Bruxelles · BEUniversità di Camerino · IT

Funding

The Integrated Stress Response in Human Islets During Early T1DU01DK127786 · NIDDK · UNIVERSITY OF CHICAGO · PI EVANS-MOLINA, CARMELLA, MIRMIRA, RAGHAVENDRA G · 2020 to 2025
$7.1M
NIDDK NIH HHS U01 DK127786
6 · The paper itself

Abstract

Metformin, a drug widely used in type 2 diabetes (T2D), has been shown to protect human β-cells exposed to gluco- and/or lipotoxic conditions and those in islets from T2D donors. We assessed whether metformin could relieve the human β-cell stress induced by pro-inflammatory cytokines (which mediate β-cells damage in type 1 diabetes, T1D) and investigated the underlying mechanisms using shotgun proteomics. Human islets were exposed to 50 U/mL interleukin-1β plus 1000 U/mL interferon-γ for 48 h, with or without 2.4 µg/mL metformin. Glucose-stimulated insulin secretion (GSIS) and caspase 3/7 activity were studied, and a shotgun label free proteomics analysis was performed. Metformin prevented the reduction of GSIS and the activation of caspase 3/7 induced by cytokines. Proteomics analysis identified more than 3000 proteins in human islets. Cytokines alone altered the expression of 244 proteins (145 up- and 99 down-regulated), while, in the presence of metformin, cytokine-exposure modified the expression of 231 proteins (128 up- and 103 downregulated). Among the proteins inversely regulated in the two conditions, we found proteins involved in vesicle motility, defense against oxidative stress (including peroxiredoxins), metabolism, protein synthesis, glycolysis and its regulation, and cytoskeletal proteins. Metformin inhibited pathways linked to inflammation, immune reactions, mammalian target of rapamycin (mTOR) signaling, and cell senescence. Some of the changes were confirmed by Western blot. Therefore, metformin prevented part of the deleterious actions of pro-inflammatory cytokines in human β-cells, which was accompanied by islet proteome modifications. This suggests that metformin, besides use in T2D, might be considered for β-cell protection in other types of diabetes, possibly including early T1D.

Indexed as

Diabetes Mellitus, Type 1Diabetes Mellitus, Type 2Islets of LangerhansMetforminCaspase 3CytokinesGlucoseHumansInsulinCaspase 3CytokinesGlucoseInsulinMetformincytokineslabel-free shotgun analysismetforminproteomicsβ-cell

Identifiers

PMID35954309
PMCPMC9368307
OpenAlexW4290703876

What OpenQuestion holds

Textfull text, public
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Registered trials

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.