Mechanisms and Applications of Metformin in Human Diseases

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 1453

Special Issue Editors


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Guest Editor
1. Program Against Cancer Therapeutic Resistance (ProCURE), Metabolism and Cancer Group, Catalan Institute of Oncology, 17005 Girona, Spain
2. Metabolism & Cancer Group, Girona Biomedical Research Institute (IDIBGI), 17190 Girona, Spain
Interests: cancer; metabolism; metformin; aging; drug development
Special Issues, Collections and Topics in MDPI journals

E-Mail Website1 Website2
Guest Editor
1. Program Against Cancer Therapeutic Resistance (ProCURE), Metabolism and Cancer Group, Catalan Institute of Oncology, 17005 Girona, Spain
2. Catalan Institute of Oncology (ICO)-Girona Biomedical Research Institute (IDIBGI), 17190 Girona, Spain
Interests: cancer; metabolism; metformin; aging; drug development
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

An ever-growing accumulation of epidemiological, pre-clinical, and clinical data is stimulating the interest in repositioning or re-tasking the biguanide metformin to treat a wide variety of diseases outside the scope of its original medical indication, type 2 diabetes (T2D). Indeed, clinical trials, such as MILES (Metformin in Longevity Study) and TAME (Targeting Aging with Metformin), have been designed to determine if metformin can directly target the aging machinery to extend healthspan. While the jack-of-all-trades behavior of metformin in human health is certainly indisputable, it remains unclear as to whether all the putative health-promoting effects of metformin are secondary to its insulin-sensitizing and glucose-lowering effects or result from other direct or indirect actions on the biological causes or hallmarks of aging and health. Moreover, there is an urgent need to clarify whether the pharmacological targets identified with supra-therapeutic concentrations of metformin may be of clinical relevance at the mechanistic level.

To encompass the remarkable breadth of ongoing investigation on metformin and aging-related diseases, research articles, short communications, review articles, as well as clinical studies covering a wide range of topics related to the therapeutic application of metformin (or metformin derivatives) in chronic diseases, hereditary genetic disorders, and rare diseases, in addition to T2D, such as chronic respiratory diseases, cardiovascular diseases, neurodegenerative diseases, cancer, as well as viral infections, including SARS-CoV-2/COVID-19, will be welcomed in this Special Issue in Pharmaceuticals. We aim to include manuscripts, including but not limited to, metformin-centered molecular mechanisms, signaling pathways, metabolism, pre-clinical models, drug formulations, analogues, drug combinations, immune response, and clinical trials. With the manuscript compendium, we will generate a molecular–clinical map of the mechanisms by which metformin not only mitigates the drivers of aging diseases but also its ability to boost (or to prevent pathogenic disruption of) the organizational and dynamical hallmarks that maintain the physiological state in human health.

Dr. Elisabet Cuyàs
Dr. Javier A. Menendez
Guest Editors

Manuscript Submission Information

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Keywords

  • metformin
  • metformin derivatives
  • molecular mechanisms of action
  • cellular mechanisms of action
  • metabolism and bioavailability
  • drug development
  • analogs
  • pre-clinical studies
  • cancer
  • hereditary cancer
  • ataxia-telangiectasia (A-T)
  • BRCA1
  • polymorphisms
  • genetic risk
  • rare diseases
  • epigenetic

Published Papers (1 paper)

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Research

19 pages, 3418 KiB  
Article
Proteomic Profiling Identifies Distinct Regulation of Proteins in Obese Diabetic Patients Treated with Metformin
by Awad Alshahrani, Ahmad Aljada, Afshan Masood, Muhammad Mujammami, Assim A. Alfadda, Mohthash Musambil, Ibrahim O. Alanazi, Mohammed Al Dubayee, Anas M. Abdel Rahman and Hicham Benabdelkamel
Pharmaceuticals 2023, 16(10), 1345; https://doi.org/10.3390/ph16101345 - 23 Sep 2023
Viewed by 1155
Abstract
Background: Obesity and type 2 diabetes mellitus (T2DM) are characterized by underlying low-grade chronic inflammation. Metformin has been used as the first line of therapy in T2DM as it decreases hepatic glucose production and glucose intestinal absorption, enhances insulin sensitivity and weight [...] Read more.
Background: Obesity and type 2 diabetes mellitus (T2DM) are characterized by underlying low-grade chronic inflammation. Metformin has been used as the first line of therapy in T2DM as it decreases hepatic glucose production and glucose intestinal absorption, enhances insulin sensitivity and weight loss, and is known to ameliorate inflammation. The mechanisms through which metformin exerts its effect remain unclear. Proteomics has emerged as a unique approach to explore the biological changes associated with diseases, including T2DM. It provides insight into the circulating biomarkers/mediators which could be utilized for disease screening, diagnosis, and prognosis. Methods: This study evaluated the proteomic changes in obese (Ob), obese diabetics (OD), and obese diabetic patients on metformin (ODM) using a 2D DIGE MALDI-TOF mass spectrometric approach. Results: Significant changes in sixteen plasma proteins (15 up and 1 down, ANOVA, p ≤ 0.05; fold change ≥ 1.5) were observed in the ODM group when compared to the Ob and OD groups. Bioinformatic network pathway analysis revealed that the majority of these altered plasma proteins are involved in distinct pathways involving acute-phase response, inflammation, and oxidative response and were centered around HNF4A, ERK, JNK, and insulin signaling pathways. Conclusions: Our study provides important information about the possible biomarkers altered by metformin treatment in obese patients with and without T2DM. These altered plasma proteins are involved in distinct pathways involving acute-phase response, inflammation, and oxidative response and were centered around HNF4A, ERK, JNK, and insulin signaling pathways. The presented proteomic profiling approach may help in identifying potential biomarkers/mediators affected by metformin treatment in T2DM and inform the understanding of metformin’s mechanisms of action. Full article
(This article belongs to the Special Issue Mechanisms and Applications of Metformin in Human Diseases)
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