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

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Genes with epigenetic alterations in human pancreatic islets impact mitochondrial function, insulin secretion, and type 2 diabetes. / Rönn, Tina; Ofori, Jones K.; Perfilyev, Alexander; Hamilton, Alexander; Pircs, Karolina; Eichelmann, Fabian; Garcia-Calzon, Sonia; Karagiannopoulos, Alexandros; Stenlund, Hans; Wendt, Anna; Volkov, Petr; Schulze, Matthias B.; Mulder, Hindrik; Eliasson, Lena; Ruhrmann, Sabrina; Bacos, Karl; Ling, Charlotte.

In: Nature Communications, Vol. 14, No. 1, 8040, 2023.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Rönn, T, Ofori, JK, Perfilyev, A, Hamilton, A, Pircs, K, Eichelmann, F, Garcia-Calzon, S, Karagiannopoulos, A, Stenlund, H, Wendt, A, Volkov, P, Schulze, MB, Mulder, H, Eliasson, L, Ruhrmann, S, Bacos, K & Ling, C 2023, 'Genes with epigenetic alterations in human pancreatic islets impact mitochondrial function, insulin secretion, and type 2 diabetes', Nature Communications, vol. 14, no. 1, 8040. https://doi.org/10.1038/s41467-023-43719-9

APA

Rönn, T., Ofori, J. K., Perfilyev, A., Hamilton, A., Pircs, K., Eichelmann, F., Garcia-Calzon, S., Karagiannopoulos, A., Stenlund, H., Wendt, A., Volkov, P., Schulze, M. B., Mulder, H., Eliasson, L., Ruhrmann, S., Bacos, K., & Ling, C. (2023). Genes with epigenetic alterations in human pancreatic islets impact mitochondrial function, insulin secretion, and type 2 diabetes. Nature Communications, 14(1), [8040]. https://doi.org/10.1038/s41467-023-43719-9

Vancouver

Rönn T, Ofori JK, Perfilyev A, Hamilton A, Pircs K, Eichelmann F et al. Genes with epigenetic alterations in human pancreatic islets impact mitochondrial function, insulin secretion, and type 2 diabetes. Nature Communications. 2023;14(1). 8040. https://doi.org/10.1038/s41467-023-43719-9

Author

Rönn, Tina ; Ofori, Jones K. ; Perfilyev, Alexander ; Hamilton, Alexander ; Pircs, Karolina ; Eichelmann, Fabian ; Garcia-Calzon, Sonia ; Karagiannopoulos, Alexandros ; Stenlund, Hans ; Wendt, Anna ; Volkov, Petr ; Schulze, Matthias B. ; Mulder, Hindrik ; Eliasson, Lena ; Ruhrmann, Sabrina ; Bacos, Karl ; Ling, Charlotte. / Genes with epigenetic alterations in human pancreatic islets impact mitochondrial function, insulin secretion, and type 2 diabetes. In: Nature Communications. 2023 ; Vol. 14, No. 1.

Bibtex

@article{40c38a2aa2744143a2de3f5644f3a2ad,

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

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.",

author = "Tina R{\"o}nn and Ofori, {Jones K.} and Alexander Perfilyev and Alexander Hamilton and Karolina Pircs and Fabian Eichelmann and Sonia Garcia-Calzon and Alexandros Karagiannopoulos and Hans Stenlund and Anna Wendt and Petr Volkov and Schulze, {Matthias B.} and Hindrik Mulder and Lena Eliasson and Sabrina Ruhrmann and Karl Bacos and Charlotte Ling",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

doi = "10.1038/s41467-023-43719-9",

language = "English",

volume = "14",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "nature publishing group",

number = "1",

}

RIS

TY - JOUR

T1 - Genes with epigenetic alterations in human pancreatic islets impact mitochondrial function, insulin secretion, and type 2 diabetes

AU - Rönn, Tina

AU - Ofori, Jones K.

AU - Perfilyev, Alexander

AU - Hamilton, Alexander

AU - Pircs, Karolina

AU - Eichelmann, Fabian

AU - Garcia-Calzon, Sonia

AU - Karagiannopoulos, Alexandros

AU - Stenlund, Hans

AU - Wendt, Anna

AU - Volkov, Petr

AU - Schulze, Matthias B.

AU - Mulder, Hindrik

AU - Eliasson, Lena

AU - Ruhrmann, Sabrina

AU - Bacos, Karl

AU - Ling, Charlotte

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-023-43719-9

DO - 10.1038/s41467-023-43719-9

M3 - Journal article

C2 - 38086799

AN - SCOPUS:85179645980

VL - 14

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 8040

ER -

ID: 377801396

Department of Biology