Metformin and insulin resistance : a review of the underlying mechanisms behind changes in GLUT4-mediated glucose transport

Herman, Rok (author), Kravos, Nika Aleksandra (author), Jensterle Sever, Mojca (author), Janež, Andrej (author), Dolžan, Vita (author)

Metformin is the most commonly used treatment to increase insulin sensitivity in insulin-resistant (IR) conditions such as diabetes, prediabetes, polycystic ovary syndrome, and obesity. There is a well-documented correlation between glucose transporter 4 (GLUT4) expression and the level of IR. Therefore, the observed increase in peripheral glucose utilization after metformin treatment most likely comes from the induction of GLUT4 expression and its increased translocation to the plasma membrane. However, the mechanisms behind this effect and the critical metformin targets are still largely undefined. The present review explores the evidence for the crucial role of changes in the expression and activation of insulin signaling pathway mediators, AMPK, several GLUT4 translocation mediators, and the effect of posttranscriptional modifications based on previously published preclinical and clinical models of metformin’s mode of action in animal and human studies. Our aim is to provide a comprehensive review of the studies in this field in order to shed some light on the complex interactions between metformin action, GLUT4 expression, GLUT4 translocation, and the observed increase in peripheral insulin sensitivity.

• Language: English
• Keywords: metformin, insulin resistance, glucose transport, glucose transporter 4
• Work type: Article
• Typology: 1.02 - Review Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2022
• Number of pages: 17 str.
• Numbering: Vol. 23, iss. 3, art. 1264
• PID: 20.500.12556/RUL-137044
• UDC: 616.379
• ISSN on article: 1422-0067
• DOI: 10.3390/ijms23031264
• COBISS.SI-ID: 94576387
• Publication date in RUL: 31.05.2022

Record is a part of a journal

• Title: International journal of molecular sciences
• Shortened title: Int. j. mol. sci.
• Publisher: MDPI
• ISSN: 1422-0067
• COBISS.SI-ID: 2779162

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 01.02.2022

Secondary language

• Language: Slovenian
• Keywords: metformin, odpornost proti insulinu, transport glukoze

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P1-0170
• Name: Molekulski mehanizmi uravnavanja celičnih procesov v povezavi z nekaterimi boleznimi pri človeku

• Funder: ARRS - Slovenian Research Agency
• Project number: P3-0298
• Name: Geni, hormonske in osebnostne spremembe pri metabolnih motnjah