Epigenetic changes in diabetes

Al-Haddad, Rami; Karnib, Nabil; Assaad, Rawad Abi; Bilen, Yara; Emmanuel, Nancy; Ghanem, Anthony; Younes, Joe; Zibara, Victor; Stephan, Joseph S.

doi:10.1016/j.neulet.2016.04.046

Cited by 49 publications

(31 citation statements)

References 85 publications

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“…MiRNAs participate in metabolic memory by targeting the mRNA of genes encoding enzymes involved in DNA methylation and those tightly regulated at the level of promoter methylation, transcription, and processing [ 102 ]. It has been shown that high glucose levels can alter post-translational histone modifications (PTHMs) and the activity of DNA methyltransferases generating irreversible changes that explain the long-term harmful effects of metabolic memory [ 103 , 104 , 105 , 106 ].…”

Section: Mechanisms Leading To T2dm and Pathophysiologymentioning

confidence: 99%

Pathophysiology of Type 2 Diabetes Mellitus

Galicia-García

Benito‐Vicente

Jebari

et al. 2020

IJMS

1,227

822

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Type 2 Diabetes Mellitus (T2DM), one of the most common metabolic disorders, is caused by a combination of two primary factors: defective insulin secretion by pancreatic β-cells and the inability of insulin-sensitive tissues to respond appropriately to insulin. Because insulin release and activity are essential processes for glucose homeostasis, the molecular mechanisms involved in the synthesis and release of insulin, as well as in its detection are tightly regulated. Defects in any of the mechanisms involved in these processes can lead to a metabolic imbalance responsible for the development of the disease. This review analyzes the key aspects of T2DM, as well as the molecular mechanisms and pathways implicated in insulin metabolism leading to T2DM and insulin resistance. For that purpose, we summarize the data gathered up until now, focusing especially on insulin synthesis, insulin release, insulin sensing and on the downstream effects on individual insulin-sensitive organs. The review also covers the pathological conditions perpetuating T2DM such as nutritional factors, physical activity, gut dysbiosis and metabolic memory. Additionally, because T2DM is associated with accelerated atherosclerosis development, we review here some of the molecular mechanisms that link T2DM and insulin resistance (IR) as well as cardiovascular risk as one of the most important complications in T2DM.

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Section: Mechanisms Leading To T2dm and Pathophysiologymentioning

confidence: 99%

Pathophysiology of Type 2 Diabetes Mellitus

Galicia-García

Benito‐Vicente

Jebari

et al. 2020

IJMS

1,227

822

View full text Add to dashboard Cite

show abstract

“…Hyperglycaemia can induce a variety of epigenetic changes that persist for days after the normalization of glucoselevels [30,34,35,36,37], mainly through the involvement of inflammatory genes [34,35]. Among the epigenetic mechanisms studied in metabolic memory, DNA methylation and post-translational histone modifications (PTHMs) are the most extensively investigated.…”

Section: Theoretical Basis For “Metabolic Memory”mentioning

confidence: 99%

“…In particular, high glucose levels can alter the activity of PTHMs and DNA methyltransferases, with irreversible changes over time. These modifications may explain the long-term harmful effects of metabolic memory [34,35,36,37]. …”

Section: Theoretical Basis For “Metabolic Memory”mentioning

confidence: 99%

The “Metabolic Memory” Theory and the Early Treatment of Hyperglycemia in Prevention of Diabetic Complications

et al. 2017

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Several epidemiological and prospective studies suggest that an early intensive control of hyperglycaemia is able to decrease the risk of diabetic micro- and macro-vascular complications. A growing body of experimental evidence supports the concept that the risk for diabetes complications may be linked to oxidative stress, non-enzymatic glycation of proteins, epigenetic changes, and chronic inflammation, laying the foundation for the “metabolic memory” theory. From a clinical point of view, this theory supports the need for a very early aggressive treatment, with the goal of normalizing metabolic control as soon as possible. It may also prove beneficial to introduce therapeutic agents that are able to reduce reactive species and glycation, in addition to presenting better control of glucose levels in patients with diabetes, in order to minimize long-term diabetes complications. In this review, we evaluate the effect of glucose intake and metabolism in the light of this theory.

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“…CGI methylation has also been suggested to be a good biomarker for the progression of cancers and diabetes 12 , 13 . A number of tumor suppressor genes are silenced by promoter CGI methylation in cancers 14 .…”

Section: Introductionmentioning

confidence: 99%

Caloric restriction delays age-related methylation drift

et al. 2017

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In mammals, caloric restriction consistently results in extended lifespan. Epigenetic information encoded by DNA methylation is tightly regulated, but shows a striking drift associated with age that includes both gains and losses of DNA methylation at various sites. Here, we report that epigenetic drift is conserved across species and the rate of drift correlates with lifespan when comparing mice, rhesus monkeys, and humans. Twenty-two to 30-year-old rhesus monkeys exposed to 30% caloric restriction since 7–14 years of age showed attenuation of age-related methylation drift compared to ad libitum-fed controls such that their blood methylation age appeared 7 years younger than their chronologic age. Even more pronounced effects were seen in 2.7–3.2-year-old mice exposed to 40% caloric restriction starting at 0.3 years of age. The effects of caloric restriction on DNA methylation were detectable across different tissues and correlated with gene expression. We propose that epigenetic drift is a determinant of lifespan in mammals.

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Epigenetic changes in diabetes

Cited by 49 publications

References 85 publications

Pathophysiology of Type 2 Diabetes Mellitus

Pathophysiology of Type 2 Diabetes Mellitus

The “Metabolic Memory” Theory and the Early Treatment of Hyperglycemia in Prevention of Diabetic Complications

Caloric restriction delays age-related methylation drift

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