TY - JOUR
T1 - Extrinsic and intrinsic factors influencing metabolic memory in type 2 diabetes
AU - Vasishta, Sampara
AU - Umakanth, Shashikiran
AU - Adiga, Prashanth
AU - Joshi, Manjunath B.
N1 - Funding Information:
We thank Manipal Academy of Higher Education, Manipal and TIFAC, Government of India for providing infrastructure. We thank Indian Council of Medical Research (ICMR), Government of India (Project ID: 5/4/1-32/2020-NCD-1 ) for funding the project. We also would like to acknowledge Dr. T.M.A Pai fellowship and senior research fellowship from Indian Council of Medical Research (ICMR), Government of India for SV.
Funding Information:
We thank Manipal Academy of Higher Education, Manipal and TIFAC, Government of India for providing infrastructure. We thank Indian Council of Medical Research (ICMR), Government of India (Project ID: 5/4/1-32/2020-NCD-1) for funding the project. We also would like to acknowledge Dr. T.M.A Pai fellowship and senior research fellowship from Indian Council of Medical Research (ICMR), Government of India for SV.
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2022/2
Y1 - 2022/2
N2 - Direct and indirect influence of pathological conditions in Type 2 Diabetes (T2D) on vasculature manifests in micro and/or macro vascular complications that act as a major source of morbidity and mortality. Although preventive therapies exist to control hyperglycemia, diabetic subjects are always at risk to accrue vascular complications. One of the hypotheses explained is ‘glycemic’ or ‘metabolic’ memory, a process of permanent epigenetic change in different cell types whereby diabetes associated vascular complications continue despite glycemic control by antidiabetic drugs. Epigenetic mechanisms including DNA methylation possess a strong influence on the association between environment and gene expression, thus indicating its importance in the pathogenesis of a complex disease such as T2D. The vascular system is more prone to environmental influences and present high flexibility in response to physiological and pathological challenges. DNA methylation based epigenetic changes during metabolic memory are influenced by sustained hyperglycemia, inflammatory mediators, gut microbiome composition, lifestyle modifications and gene-nutrient interactions. Hence, understanding underlying mechanisms in manifesting vascular complications regulated by DNA methylation is of high clinical importance. The review provides an insight into various extrinsic and intrinsic factors influencing the regulation of DNA methyltransferases contributing to the pathogenesis of vascular complications during T2D.
AB - Direct and indirect influence of pathological conditions in Type 2 Diabetes (T2D) on vasculature manifests in micro and/or macro vascular complications that act as a major source of morbidity and mortality. Although preventive therapies exist to control hyperglycemia, diabetic subjects are always at risk to accrue vascular complications. One of the hypotheses explained is ‘glycemic’ or ‘metabolic’ memory, a process of permanent epigenetic change in different cell types whereby diabetes associated vascular complications continue despite glycemic control by antidiabetic drugs. Epigenetic mechanisms including DNA methylation possess a strong influence on the association between environment and gene expression, thus indicating its importance in the pathogenesis of a complex disease such as T2D. The vascular system is more prone to environmental influences and present high flexibility in response to physiological and pathological challenges. DNA methylation based epigenetic changes during metabolic memory are influenced by sustained hyperglycemia, inflammatory mediators, gut microbiome composition, lifestyle modifications and gene-nutrient interactions. Hence, understanding underlying mechanisms in manifesting vascular complications regulated by DNA methylation is of high clinical importance. The review provides an insight into various extrinsic and intrinsic factors influencing the regulation of DNA methyltransferases contributing to the pathogenesis of vascular complications during T2D.
UR - http://www.scopus.com/inward/record.url?scp=85119036008&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85119036008&partnerID=8YFLogxK
U2 - 10.1016/j.vph.2021.106933
DO - 10.1016/j.vph.2021.106933
M3 - Review article
AN - SCOPUS:85119036008
SN - 1537-1891
VL - 142
JO - Vascular Pharmacology
JF - Vascular Pharmacology
M1 - 106933
ER -