Your browser has javascript turned off or blocked. This will lead to some parts of our website to not work properly or at all. Turn on javascript for best performance.

The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Default user image.

Alexander Perfilyev

Assistant researcher

Default user image.

Diabetes medication associates with DNA methylation of metformin transporter genes in the human liver

Author

  • Sonia García-Calzón
  • Alexander Perfilyev
  • Ville Männistö
  • Vanessa de Mello
  • Emma A Nilsson
  • Jussi Pihlajamäki
  • Charlotte Ling

Summary, in English

Background: Given that metformin is the most common pharmacological therapy for type 2 diabetes, understanding the function of this drug is of great importance. Hepatic metformin transporters are responsible for the pharmacologic action of metformin. However, epigenetics in genes encoding metformin transporters has not been fully elucidated. We examined the DNA methylation of these genes in the liver of subjects with type 2 diabetes and tested whether epigenetic alterations associate with diabetes medication, i.e., metformin or insulin plus metformin treatment. Results: DNA methylation in OCT1 encoded by SLC22A1, OCT3 encoded by SLC22A3, and MATE1 encoded by SLC47A1 was assessed in the human liver. Lower average and promoter DNA methylation of SLC22A1, SLC22A3, and SLC47A1 was found in diabetic subjects receiving just metformin, compared to those who took insulin plus metformin or no diabetes medication. Moreover, diabetic subjects receiving just metformin had a similar DNA methylation pattern in these genes compared to non-diabetic subjects. Notably, DNA methylation was also associated with gene expression, glucose levels, and body mass index, i.e., higher SLC22A3 methylation was related to lower SLC22A3 expression and to insulin plus metformin treatment, higher fasting glucose levels and higher body mass index. Importantly, metformin treatment did also directly decrease DNA methylation of SLC22A1 in hepatocytes cultured in vitro. Conclusions: Our study supports that metformin decreases DNA methylation of metformin transporter genes in the human liver. Moreover, higher methylation levels in these genes associate with hyperglycaemia and obesity.

Department/s

  • Diabetes - Epigenetics
  • EXODIAB: Excellence of Diabetes Research in Sweden

Publishing year

2017-09-21

Language

English

Pages

1-9

Publication/Series

Clinical Epigenetics

Volume

9

Issue

1

Document type

Journal article

Publisher

BioMed Central (BMC)

Topic

  • Endocrinology and Diabetes

Keywords

  • Diabetes medication
  • Epigenetics
  • Liver
  • Metformin
  • Organic cation transporters
  • Type 2 diabetes

Status

Published

Research group

  • Diabetes - Epigenetics
  • LUDC (Lund University Diabetes Centre)

ISBN/ISSN/Other

  • ISSN: 1868-7075