Evidence map›Paper›PMID 34502359›Full record

ReviewInternational journal of molecular sciences2021

New Insight into the Effects of Metformin on Diabetic Retinopathy, Aging and Cancer: Nonapoptotic Cell Death, Immunosuppression, and Effects beyond the AMPK Pathway.

Sheng-Kai Hsu, Kai-Chun Cheng, Miracle Oluebube Mgbeahuruike, Yi-Hsiung Lin, Chang-Yi Wu, Hui-Min David Wang, Chia-Hung Yen, Chien-Chih Chiu, Shwu-Jiuan Sheu

Open access · goldFull text readReview
In one paragraph

Review in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
4.1field-weighted citation impact, top 5% 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.

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

47 citing papers in PubMed, 78 citations in OpenAlex.

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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

9 authors at 3 institutions in 1 country.

Sheng-Kai HsuDepartment of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Kai-Chun ChengDepartment of Ophthalmology, Kaohsiung Municipal Siaogang Hospital, Kaohsiung 812, Taiwan.ORCID 0000-0002-1240-4219
Miracle Oluebube MgbeahuruikeDepartment of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Yi-Hsiung LinDivision of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.ORCID 0000-0003-2232-9037
Chang-Yi WuDepartment of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Hui-Min David WangGraduate Institute of Biomedical Engineering, National Chung Hsing University, Taichung 402, Taiwan.ORCID 0000-0002-4692-4917
Chia-Hung YenGraduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan.ORCID 0000-0002-6939-5528
Chien-Chih ChiuDepartment of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan.ORCID 0000-0001-7307-2468
Shwu-Jiuan SheuDepartment of Ophthalmology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.ORCID 0000-0003-2644-2475
Kaohsiung Medical University · TWNational Sun Yat-sen University · TWNational Chung Hsing University · TW

Funding

NSYSU-KMU NSYSUKMU110-P024the Kaohsiung Medical University Research Center, Taiwan KMU-TC109A04the Ministry of Science and Technology, Taiwan 109-2314-B-037-069-MY3the Ministry of Science and Technology, Taiwan MOST 109-2313-B-037-001the Ministry of Science and Technology, Taiwan MOST 109-2314-B-037 -024
6 · The paper itself

Abstract

Under metabolic stress conditions such as hypoxia and glucose deprivation, an increase in the AMP:ATP ratio activates the AMP-activated protein kinase (AMPK) pathway, resulting in the modulation of cellular metabolism. Metformin, which is widely prescribed for type 2 diabetes mellitus (T2DM) patients, regulates blood sugar by inhibiting hepatic gluconeogenesis and promoting insulin sensitivity to facilitate glucose uptake by cells. At the molecular level, the most well-known mechanism of metformin-mediated cytoprotection is AMPK pathway activation, which modulates metabolism and protects cells from degradation or pathogenic changes, such as those related to aging and diabetic retinopathy (DR). Recently, it has been revealed that metformin acts via AMPK- and non-AMPK-mediated pathways to exert effects beyond those related to diabetes treatment that might prevent aging and ameliorate DR. This review focuses on new insights into the anticancer effects of metformin and its potential modulation of several novel types of nonapoptotic cell death, including ferroptosis, pyroptosis, and necroptosis. In addition, the antimetastatic and immunosuppressive effects of metformin and its hypothesized mechanism are also discussed, highlighting promising cancer prevention strategies for the future.

Indexed as

AgingAMP-Activated Protein KinasesBlood GlucoseCell DeathDiabetes Mellitus, Type 2Diabetic RetinopathyGluconeogenesisGlucoseHumansHypoglycemic AgentsImmunosuppression TherapyInsulinInsulin ResistanceMetforminNeoplasmsProtein Serine-Threonine KinasesAMP-Activated Protein KinasesBlood GlucoseGlucoseHypoglycemic AgentsInsulinMetforminProtein Serine-Threonine Kinasesagingbiguanidescancer chemopreventionimmunosuppressionmetastasismetforminnonapoptotic cell death

Identifiers

PMID34502359
PMCPMC8430477
OpenAlexW3196917655

What OpenQuestion holds

Textfull text, public
LicenceCC BY
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 OpenQuestion graph.