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Role of epigenomic mechanisms in the onset and management of insulin resistance

  • Andrea G. Izquierdo
  • Ana B. CrujeirasEmail author
Article

Abstract

The prevalence of insulin resistance (IR) is increasing rapidly worldwide and it is a relevant health problem because it is associated with several diseases, such as type 2 diabetes, cardiovascular disorders and cancer. Understanding the mechanisms involved in IR onset and progression will open new avenues for identifying biomarkers for preventing and treating IR and its co-diseases. Epigenetic mechanisms such as DNA methylation are important factors that mediate the environmental effect in the genome by regulating gene expression and consequently its effect on the phenotype and the development of disease. Taking into account that IR results from a complex interplay between genes and the environment and that epigenetic marks are reversible, disentangling the relationship between IR and epigenetics will provide new tools to improve the management and prevention of IR. Here, we review the current scientific evidence regarding the association between IR and epigenetic markers as mechanisms involved in IR development and potential management.

Keywords

DNA methylation Non-coding RNA Glucose homeostasis Insulin sensitivity Type 2 diabetes Biomarkers 

Abbreviations

5mC

5-methylcytosine

ADAM2

ADAM metallopeptidase domain 2

ADCY9

adenylate cyclase 9

BS

bisulphite sequencing

C

cytosine

CERs

ceramides

COL11A2

collagen type XI alpha 2 chain

COL5A1

collagen type V alpha 1 chain

COL9A1

collagen, type IX, alpha 1

DAGs

diacylglycerols

DMCpG

differentially methylated CpG

DNA

deoxyribonucleic acid

DNMTs

DNA methyltransferases

ER

endoplasmic reticulum

FAM123C

family with sequence similarity 123C

FHL2

four and a half LIM domains 2

FTO

FTO alpha-ketoglutarate dependent dioxygenase

GAB1

GRB2 associated binding protein 1

GATA4

GATA binding protein 4

GDM

glucose disposal metabolizable glucose

GDR

rate of whole-body glucose disposal

GLUT-4

glucose transporter type 4

GO

gene ontology

HDACM

histone deacetylase

HHEX

hematopoietically expressed homeobox

HOMA-IR

Homeostatic Model Assessment for Insulin Resistance

IGF2BP1

insulin like growth factor 2 mRNA binding protein 1

IGF2BP2

insulin like growth factor 2 mRNA binding protein 2

IL

interleukins

IR

insulin resistance

IRS

insulin receptor substrate

IS

insulin-sensitive

JAZF1

JAZF zinc finger 1

KCNJ11

potassium voltage-gated channel subfamily J member 11

KCNQ1

potassium voltage-gated channel subfamily Q member

KLF14

Kruppel like factor 14

lncRNA

long non-coding RNA

MAM

membranes associated with mitochondria

MBD

methyl-CpG-binding domain

miRNA

microRNA

MS

metabolic syndrome

MUC4

mucin 4, cell surface associated

NAFLD

non-alcoholic fatty liver disease

ncRNAs

non-coding RNA

NOTCH2

notch receptor 2

PCOD

polycystic ovarian disease

PCR

polymerase chain reaction

PFKFB3

6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3

PI3K

Phosphoinositide 3-kinase

PTMs

post-translational histone modifications

PTPRJ

protein tyrosine phosphatase receptor type J

SAT

subcutaneous adipose tissue

SIRTs

Sirtuins

T2D

type 2 diabetes mellitus

TBX5

T-box 5

TCF7L2

transcription factor 7 like 2

TET1

tet methylcytosine dioxygenase 1

THADA

THADA armadillo repeat containing

TNF-α

tumour necrosis factor alfa

VAT

visceral adipose tissue

WFS1

wolframin ER transmembrane glycoprotein

ZNF518B

zinc finger protein 518B

ZNF714

zinc finger protein 714

Notes

Acknowledgements

The research of the author’s lab is supported by Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBERobn) and grants from the Instituto de Salud Carlos III-ISCIII (PI17/01287, CP17/00088) co-financed by the European Regional Development Fund (FEDER). Ana B Crujeiras is funded by a research contract “Miguel Servet” (CP17/00088) from the ISCIII.

Compliance with ethical standards

Competing interest disclosure

The authors declare that they have no conflict of interest.

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Epigenomics in Endocrinology and Nutrition group, Instituto de Investigacion Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS/SERGAS)Santiago de CompostelaSpain
  2. 2.CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERobn)MadridSpain

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