Novel epigenetic-sensitive clinical challenges both in type 1 and type 2 diabetes

Linda Sommese, Giuditta Benincasa, Michele Lanza, Antonio Sorriento, Concetta Schiano, Roberta Lucchese, Roberto Alfano, Giovanni Francesco Nicoletti, Claudio Napoli

Research output: Contribution to journalReview article

Abstract

Background: Epigenetics modulated tissue-specific gene expression during the onset of type 1 and type 2 diabetes and their complications. Methods: We searched the PubMed recent studies about the main epigenetic tags involved in type 1 and type 2 diabetes onset and their clinical complications. PubMed studies about the epigenetic tags involved in type 1 and 2 diabetes onset was searched. Results: The epigenetic methylation maps of cord blood samples highlighted differences in the methylation status of CpG sites within the MHC genes between carriers of diabetes type 1 DR3-DQ2 and DR4-DQ8 risk haplotypes. β cell-derived unmethylated INS DNA showed the decline of β-cell mass preserving insulin secretion. Differentially methylated regions in pancreatic islets from type 2 diabetes covered PDX1, TCF7L2, and ADCY5 promoters during islet dysfunction. The recruitment of SET7 and SUV39H1 histone methyltransferases and LSD-1 lysine-specific demethylase-1 at NF-kβ-p65 promoter in vascular cells was involved in coronary heart disease. Neutrophil extracellular trap, activated by protein arginine deiminase-4, impaired wound healing from diabetic foot ulcers. MiR-199a-3p over-expression induced coagulative cascade, swelling and pain by a down-regulation of SERPIN-E2 in diabetic peripheral neuropathy. A DNA hypo-methylation and histone hyper-acetylation at MIOX promoter led an overexpression of ROS, fibronectin, HIF-1α and NOX-4 associated with diabetic tubulopathy. A hypo-methylation of H3K4 at SOD2 promoter by LSD-1 increased ROS causing diabetic retinopathy. Conclusions: Epigenetics played a relevant role in prevention, diagnosis, and treatment of diabetes.

Original languageEnglish
Pages (from-to)1076-1084
Number of pages9
JournalJournal of Diabetes and its Complications
Volume32
Issue number11
DOIs
Publication statusPublished - Nov 1 2018

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Keywords

  • Coronary heart disease
  • Diabetes type 1 and type 2
  • Diabetic foot ulcer
  • Diabetic peripheral neuropathy
  • Epigenetics

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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