Epigenetic modifications in pancreas development, diabetes, and therapeutics

Kaimala, Suneesh; Kumar, Challagandla Anil; Allouh, Mohammed Z.; Ansari, Suraiya A.; Emerald, Bright Starling

doi:10.1002/med.21878

Cited by 23 publications

(16 citation statements)

References 162 publications

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“…We determined gene methylation in DNA from cells taken from peripheral blood because epigenetic biomarkers in blood have more clinical potential than pancreatic islets as islets cannot be non-invasively assessed. There is evidence that DNA methylation changes in blood cells reflect the epigenetic changes identified in human pancreatic islets and can reflect insulin secretion [ 39 , 40 , 41 , 42 , 43 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of Inulin Intervention on Metabolic Control and Methylation of INS and IRS1 Genes in Patients with Type 2 Diabetes Mellitus

et al. 2022

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Background and Aims: Currently, treatments are being sought to improve the control of type II diabetes mellitus (T2DM), and inulin has been shown to be effective in reducing glucose levels and other metabolic control parameters. These effects on metabolic control may be associated with changes in the epigenetic modulation of genes of the insulin pathway. Therefore, our objective is to determine the effect of agave inulin in metabolic control parameters and in INS and IRS1 genes’ methylation in T2DM patients. Methods: This was a longitudinal experimental study with 67 Mexican participants who received an intervention of inulin agave (10 g daily) for 2 months. The methylation of the INS and IRS1 genes was determined by MSP. Results: For the INS gene, we found a significant decrease in the proportions of T2DM patients with methylated DNA after inulin intervention (p = 0.0001). In contrast, the difference in the proportions of the unmethylated IRS1 gene before and after the inulin intervention was not significant (p = 0.79). On the other hand, we observed changes in the number of T2DM patients’ recommended categories for metabolic control depending on the methylation of INS and IRS1 genes before and after treatment with inulin. Conclusion: For the first time, we report the modification in the methylation of two genes, INS and IRS1, of the insulin pathway and provide information on the possible relevant role of epigenetics as a key factor in positive changes in metabolic control parameters by inulin intake in T2DM patients.

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Section: Discussionmentioning

confidence: 99%

Effect of Inulin Intervention on Metabolic Control and Methylation of INS and IRS1 Genes in Patients with Type 2 Diabetes Mellitus

et al. 2022

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“…One of the essential issues of diabetic stimuli triggers some epigenetic modifications to be the basis of metabolic memory [ 90 , 91 , 92 ]. Nevertheless, there remains a lack of information regarding epigenetic factors and the mechanism related to gene modification; this is probably the rationality behind the rapid growth and energetic field for new mechanisms and therapeutic targets [ 93 ].…”

Section: Is There a Possible Therapeutic Related To Epigenetics?mentioning

confidence: 99%

Epigenetics in Obesity and Diabetes Mellitus: New Insights

et al. 2023

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A long-term complication of obesity is the development of type 2 diabetes (T2D). Patients with T2D have been described as having epigenetic modifications. Epigenetics is the post-transcriptional modification of DNA or associated factors containing genetic information. These environmentally-influenced modifications, maintained during cell division, cause stable changes in gene expression. Epigenetic modifications of T2D are DNA methylation, acetylation, ubiquitylation, SUMOylation, and phosphorylation at the lysine residue at the amino terminus of histones, affecting DNA, histones, and non-coding RNA. DNA methylation has been shown in pancreatic islets, adipose tissue, skeletal muscle, and the liver. Furthermore, epigenetic changes have been observed in chronic complications of T2D, such as diabetic nephropathy, diabetic retinopathy, and diabetic neuropathy. Recently, a new drug has been developed which acts on bromodomains and extraterminal (BET) domain proteins, which operate like epigenetic readers and communicate with chromatin to make DNA accessible for transcription by inhibiting them. This drug (apabetalone) is being studied to prevent major adverse cardiovascular events in people with T2D, low HDL cholesterol, chronic kidney failure, and recent coronary events. This review aims to describe the relationship between obesity, long-term complications such as T2D, and epigenetic modifications and their possible treatments.

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“…Epigenetic regulation of pancreatic development and diseases, especially DNA methylation and histone modification, has been reviewed in detail elsewhere (Arnes & Sussel, 2015; Golson & Kaestner, 2017; Kaimala, Kumar, Allouh, Ansari, & Emerald, 2022; Quilichini & Haumaitre, 2015). Here we briefly summarize how these two epigenetic mechanisms contribute to pancreatic birth defects (Figure 1).…”

Section: Disruption Of Epigenetic Regulation Can Cause Developmental ...mentioning

confidence: 99%

The role of noncoding RNAs in pancreatic birth defects

Yang

Parchem

2023

Birth Defects Research

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Congenital defects in the pancreas can cause severe health issues such as pancreatic cancer and diabetes which require lifelong treatment. Regenerating healthy pancreatic cells to replace malfunctioning cells has been considered a promising cure for pancreatic diseases including birth defects. However, such therapies are currently unavailable in the clinic. The developmental gene regulatory network underlying pancreatic development must be reactivated for in vivo regeneration and recapitulated in vitro for cell replacement therapy. Thus, understanding the mechanisms driving pancreatic development will pave the way for regenerative therapies. Pancreatic progenitor cells are the precursors of all pancreatic cells which use epigenetic changes to control gene expression during differentiation to generate all of the distinct pancreatic cell types. Epigenetic changes involving DNA methylation and histone modifications can be controlled by noncoding RNAs (ncRNAs). Indeed, increasing evidence suggests that ncRNAs are indispensable for proper organogenesis. Here, we summarize recent insight into the role of ncRNAs in the epigenetic regulation of pancreatic development. We further discuss how disruptions in ncRNA biogenesis and expression lead to developmental defects and diseases. This review summarizes in vivo data from animal models and in vitro studies using stem cell differentiation as a model for pancreatic development.

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Epigenetic modifications in pancreas development, diabetes, and therapeutics

Abstract: A recent International Diabetes Federation report suggests that more than 463 million people between 20 and 79 years have diabetes. Of the 20 million women affected by hyperglycemia during pregnancy, 84% have gestational

Cited by 23 publications

References 162 publications

Effect of Inulin Intervention on Metabolic Control and Methylation of INS and IRS1 Genes in Patients with Type 2 Diabetes Mellitus

Effect of Inulin Intervention on Metabolic Control and Methylation of INS and IRS1 Genes in Patients with Type 2 Diabetes Mellitus

Epigenetics in Obesity and Diabetes Mellitus: New Insights

The role of noncoding RNAs in pancreatic birth defects

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