ArticleG3 (Bethesda, Md.)2019
Metformin Affects Heme Function as a Possible Mechanism of Action.
Article in G3 (Bethesda, Md.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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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.
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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.
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Who cites it
14 citing papers in PubMed, 17 citations in OpenAlex.
- Emerging role of plant-based compounds as ferroptosis modulators in breast cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Polygenic prediction of human longevity on the supposition of pervasive pleiotropy.Scientific reports · 2024Article
- Polygenic prediction of human longevity on the supposition of pervasive pleiotropy.medRxiv : the preprint server for health sciences · 2023Article
- Metformin in therapeutic applications in human diseases: its mechanism of action and clinical study.Molecular biomedicine · 2022Review
- Metabolic Action of Metformin.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Role of Iron in Aging Related Diseases.Antioxidants (Basel, Switzerland) · 2022Article
- Unravelling genetic components of longevity.Nature aging · 2022Article
- Iron: an underrated factor in aging.Aging · 2021Article
- An Analysis of the Multifaceted Roles of Heme in the Pathogenesis of Cancer and Related Diseases.Cancers · 2021Review
- Cellular and Molecular Mechanisms of Metformin Action.Endocrine reviews · 2021Review
- Clinical study on polycystic ovary syndrome treated with Diane-35 and Pioglitazone.American journal of translational research · 2021Article
- Article
- Commentary: Lactate-Induced Glucose Output Is Unchanged by Metformin at a Therapeutic Concentration-A Mass Spectrometry Imaging Study of the Perfused Rat Liver.Frontiers in pharmacology · 2019Article
- Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metformin elicits pleiotropic effects that are beneficial for treating diabetes, as well as particular cancers and aging. In spite of its importance, a convincing and unifying mechanism to explain how metformin operates is lacking. Here we describe investigations into the mechanism of metformin action through heme and hemoprotein(s). Metformin suppresses heme production by 50% in yeast, and this suppression requires mitochondria function, which is necessary for heme synthesis. At high concentrations comparable to those in the clinic, metformin also suppresses heme production in human erythrocytes, erythropoietic cells and hepatocytes by 30-50%; the heme-targeting drug artemisinin operates at a greater potency. Significantly, metformin prevents oxidation of heme in three protein scaffolds, cytochrome c, myoglobin and hemoglobin, with Kd values < 3 mM suggesting a dual oxidation and reduction role in the regulation of heme redox transition. Since heme- and porphyrin-like groups operate in diverse enzymes that control important metabolic processes, we suggest that metformin acts, at least in part, through stabilizing appropriate redox states in heme and other porphyrin-containing groups to control cellular metabolism.
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