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

5 Citations (Scopus)

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

Fingerprint

Type 1 Diabetes Mellitus
Epigenomics
Type 2 Diabetes Mellitus
Methylation
Lysergic Acid Diethylamide
PubMed
Diabetic Foot
Diabetic Neuropathies
Peripheral Nervous System Diseases
Diabetic Retinopathy
DNA Methylation
Diabetes Complications
Acetylation
Fetal Blood
Islets of Langerhans
Fibronectins
Histones
Wound Healing
Haplotypes
Lysine

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

Cite this

Novel epigenetic-sensitive clinical challenges both in type 1 and type 2 diabetes. / Sommese, Linda; Benincasa, Giuditta; Lanza, Michele; Sorriento, Antonio; Schiano, Concetta; Lucchese, Roberta; Alfano, Roberto; Nicoletti, Giovanni Francesco; Napoli, Claudio.

In: Journal of Diabetes and its Complications, Vol. 32, No. 11, 01.11.2018, p. 1076-1084.

Research output: Contribution to journalReview article

Sommese, L, Benincasa, G, Lanza, M, Sorriento, A, Schiano, C, Lucchese, R, Alfano, R, Nicoletti, GF & Napoli, C 2018, 'Novel epigenetic-sensitive clinical challenges both in type 1 and type 2 diabetes', Journal of Diabetes and its Complications, vol. 32, no. 11, pp. 1076-1084. https://doi.org/10.1016/j.jdiacomp.2018.08.012
Sommese, Linda ; Benincasa, Giuditta ; Lanza, Michele ; Sorriento, Antonio ; Schiano, Concetta ; Lucchese, Roberta ; Alfano, Roberto ; Nicoletti, Giovanni Francesco ; Napoli, Claudio. / Novel epigenetic-sensitive clinical challenges both in type 1 and type 2 diabetes. In: Journal of Diabetes and its Complications. 2018 ; Vol. 32, No. 11. pp. 1076-1084.
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T1 - Novel epigenetic-sensitive clinical challenges both in type 1 and type 2 diabetes

AU - Sommese, Linda

AU - Benincasa, Giuditta

AU - Lanza, Michele

AU - Sorriento, Antonio

AU - Schiano, Concetta

AU - Lucchese, Roberta

AU - Alfano, Roberto

AU - Nicoletti, Giovanni Francesco

AU - Napoli, Claudio

PY - 2018/11/1

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N2 - 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.

AB - 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.

KW - Coronary heart disease

KW - Diabetes type 1 and type 2

KW - Diabetic foot ulcer

KW - Diabetic peripheral neuropathy

KW - Epigenetics

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