Genes with epigenetic alterations in human pancreatic islets impact mitochondrial function, insulin secretion, and type 2 diabetes

Tina Rönn, Jones K. Ofori, Alexander Perfilyev, Alexander Hamilton, Karolina Pircs, Fabian Eichelmann, Sonia Garcia-Calzon, Alexandros Karagiannopoulos, Hans Stenlund, Anna Wendt, Petr Volkov, Matthias B. Schulze, Hindrik Mulder, Lena Eliasson, Sabrina Ruhrmann, Karl Bacos and Charlotte Ling ()
Additional contact information
Tina Rönn: Scania University Hospital
Jones K. Ofori: Scania University Hospital
Alexander Perfilyev: Scania University Hospital
Alexander Hamilton: Scania University Hospital
Karolina Pircs: Lund University
Fabian Eichelmann: German Institute of Human Nutrition Potsdam-Rehbruecke
Sonia Garcia-Calzon: Scania University Hospital
Alexandros Karagiannopoulos: Scania University Hospital
Hans Stenlund: Umeå University
Anna Wendt: Scania University Hospital
Petr Volkov: Scania University Hospital
Matthias B. Schulze: German Institute of Human Nutrition Potsdam-Rehbruecke
Hindrik Mulder: Scania University Hospital
Lena Eliasson: Scania University Hospital
Sabrina Ruhrmann: Scania University Hospital
Karl Bacos: Scania University Hospital
Charlotte Ling: Scania University Hospital

Nature Communications, 2023, vol. 14, issue 1, 1-21

Abstract: Abstract Epigenetic dysregulation may influence disease progression. Here we explore whether epigenetic alterations in human pancreatic islets impact insulin secretion and type 2 diabetes (T2D). In islets, 5,584 DNA methylation sites exhibit alterations in T2D cases versus controls and are associated with HbA1c in individuals not diagnosed with T2D. T2D-associated methylation changes are found in enhancers and regions bound by β-cell-specific transcription factors and associated with reduced expression of e.g. CABLES1, FOXP1, GABRA2, GLR1A, RHOT1, and TBC1D4. We find RHOT1 (MIRO1) to be a key regulator of insulin secretion in human islets. Rhot1-deficiency in β-cells leads to reduced insulin secretion, ATP/ADP ratio, mitochondrial mass, Ca2+, and respiration. Regulators of mitochondrial dynamics and metabolites, including L-proline, glycine, GABA, and carnitines, are altered in Rhot1-deficient β-cells. Islets from diabetic GK rats present Rhot1-deficiency. Finally, RHOT1methylation in blood is associated with future T2D. Together, individuals with T2D exhibit epigenetic alterations linked to mitochondrial dysfunction in pancreatic islets.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-43719-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43719-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-43719-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().