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

  • Andrea G. Izquierdo
  • Ana B. CrujeirasEmail author


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.


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





ADAM metallopeptidase domain 2


adenylate cyclase 9


bisulphite sequencing






collagen type XI alpha 2 chain


collagen type V alpha 1 chain


collagen, type IX, alpha 1




differentially methylated CpG


deoxyribonucleic acid


DNA methyltransferases


endoplasmic reticulum


family with sequence similarity 123C


four and a half LIM domains 2


FTO alpha-ketoglutarate dependent dioxygenase


GRB2 associated binding protein 1


GATA binding protein 4


glucose disposal metabolizable glucose


rate of whole-body glucose disposal


glucose transporter type 4


gene ontology


histone deacetylase


hematopoietically expressed homeobox


Homeostatic Model Assessment for Insulin Resistance


insulin like growth factor 2 mRNA binding protein 1


insulin like growth factor 2 mRNA binding protein 2




insulin resistance


insulin receptor substrate




JAZF zinc finger 1


potassium voltage-gated channel subfamily J member 11


potassium voltage-gated channel subfamily Q member


Kruppel like factor 14


long non-coding RNA


membranes associated with mitochondria


methyl-CpG-binding domain




metabolic syndrome


mucin 4, cell surface associated


non-alcoholic fatty liver disease


non-coding RNA


notch receptor 2


polycystic ovarian disease


polymerase chain reaction


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


Phosphoinositide 3-kinase


post-translational histone modifications


protein tyrosine phosphatase receptor type J


subcutaneous adipose tissue




type 2 diabetes mellitus


T-box 5


transcription factor 7 like 2


tet methylcytosine dioxygenase 1


THADA armadillo repeat containing


tumour necrosis factor alfa


visceral adipose tissue


wolframin ER transmembrane glycoprotein


zinc finger protein 518B


zinc finger protein 714



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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