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The co-activator-associated arginine methyltransferase 1 (CARM1) gene is overexpressed in type 2 diabetes

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Abstract

Purpose

We examined the expression of a panel of epigenetic enzymes catalyzing histone tails post-transcriptional modifications, together with effectors of metabolic and inflammatory alterations, in type 2 diabetes.

Methods

Cross-sectional, case–control study of 21 people with type 2 diabetes and 21 matched controls. Total RNA was extracted from white cells and reverse transcribed. PCR primer assays for 84 key genes encoding enzymes known to modify genomic DNA and histones were performed. Western blot was performed on lysates using primary antibodies for abnormally expressed enzymes. Hormones and cytokines were measured by multiplex kits. A Bayesian network was built to investigate the relationships between epigenetic, cytokine, and endocrine variables.

Results

Co-activator-associated aRginine Methyltransferase 1 (CARM1) expression showed a five-fold higher median value, matched by higher protein levels, among patients who also had increased GIP, IL-4, IL-7, IL-13, IL-17, FGF basic, G-CSF, IFN-γ, and TNFα and decreased IP-10. In a Bayesian network approach, CARM1 expression showed a conditional dependence on diabetes, but was independent of all other variables nor appeared to influence any.

Conclusions

Increased CARM1 expression in type 2 diabetes suggests that epigenetic mechanisms are altered in human diabetes. The impact of lifestyle and pharmacological treatment on regulation of this enzyme should be further investigated.

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Abbreviations

CARM1:

Co-activator-associated aRginine Methyltransferase 1

FGF:

Fibroblast growth factor

G-CSF :

Granulocyte colony-stimulating factor

GIP:

Gastric inhibitory polypeptide or glucose-dependent insulinotropic peptide

GLP-1:

Glucagon-like peptide 1

IFN-γ:

Interferon gamma

IP-10:

Interferon-γ-inducible protein 10

IL-1ra:

Interleukin-1 receptor antagonist

IL-1β:

InterLeukin 1 beta

IL-4 :

InterLeukin 4

IL-5:

InterLeukin 5

IL-6 :

InterLeukin 6

IL-7 :

InterLeukin 7

IL-9:

InterLeukin 9

IL-10 :

InterLeukin 10

IL-12 :

InterLeukin 12

IL-13 :

InterLeukin 13

IL-17 :

InterLeukin 17

MCP-1 :

Monocyte chemoattractant protein-1

MIP-1a :

Macrophage inflammatory protein 1a

NFkB :

Nuclear factor kappa-light-chain-enhancer of activated B cells

PAI-1 :

Plasminogen activator inhibitor-1

PDGF:

Platelet-derived growth factor

TNF-α :

Tumor necrosis factor alpha

VEGF:

Vascular endothelial growth factor

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Funding

This work was supported by Progetto Finalizzato RF 2010 230456 from the Italian Ministry of Health, and Departmental funds (Fondi ex-60%-2015) from the Department of Medical Sciences at Turin University.

Author contributions

M.P. and M.T. conceived the study, researched data, and drafted the manuscript. C.A., F.B., P.F., S.M., L.A., M.C., and P.U. participated in data acquisition. F.B., P.B., and F.C. contributed to analysis and interpretation of data and reviewed/edited the manuscript. G.G. and M.D. contributed to the discussion and reviewed/edited the manuscript. All authors gave their final approval to this version of the manuscript.

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Authors and Affiliations

  1. Department of Medical Sciences, Laboratory of Clinical Pedagogy, University of Turin, Turin, Italy

    Massimo Porta, Cristina Amione, Federica Barutta, Paolo Fornengo, Stefano Merlo, Gabriella Gruden, Marilena Durazzo & Marina Trento

  2. National Research Council, URT of the Institute of Experimental Endocrinology Oncology “G. Salvatore”, Naples, Italy

    Luigi Albano, Marco Ciccarelli, Paola Ungaro & Francesco Beguinot

  3. Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy

    Francesco Beguinot

  4. Department of Clinical and Biological Sciences, University of Turin, Turin, Italy

    Paola Berchialla

  5. Department of Public Health and Paediatric Sciences, University of Turin, Turin, Italy

    Franco Cavallo

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  1. Massimo Porta
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  2. Cristina Amione
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  3. Federica Barutta
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Correspondence to Massimo Porta.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Porta, M., Amione, C., Barutta, F. et al. The co-activator-associated arginine methyltransferase 1 (CARM1) gene is overexpressed in type 2 diabetes. Endocrine 63, 284–292 (2019). https://doi.org/10.1007/s12020-018-1740-z

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