Question

What is the mechanism of DNA methylation, or dysregulation/dysfunction, that occurs in the cardio-metabolic condition mentioned...

What is the mechanism of DNA methylation, or dysregulation/dysfunction, that occurs in the cardio-metabolic condition mentioned of Type II diabetes? Are there any treatments related to this knowledge that could be applied?

Homework Answers

Answer #1

Type2 diabetes (T2D) or non- insulin dependent diabetes is a medical condition in which either the pancreatic beta cells don't produce enough insulin or the body cells not able to respond to it. Insulin is required to move glucose inside the cells, such that normal blood glucose level can be maintained.

Role of epigenetics specially DNA methylation has been shown to be related with pathogenesis of T2D.

Alterations in DNA methylation-

  • reduces insulin secretion via affecting genes such as- PPARGC1A, PDX1, INS.
  • increases insulin resistance via affecting genes such as- NDUFB, OXPHOX, IGFBP1, IGFBP7.

Hypermethylation of PPARGC1A, a gene promotor an present in pancreatic islets, reduces its expression and hence is known to be associated with reduced insulin secretion.

Hypermethylation of PDX-1, a transcription factor present in pancreatic islets, reduces its expression and hence is known to be associated with reduced insulin secretion.

NDUFB is a promotor of ubiquinone oxidoreductase subunits, present in skeletal muscles. Hypermethylation of this protein reduced its expression and hence is associated with reduced glucose uptake by skeletal cells.

Cox7A encodes OXPHOS, and oxidative phosphorylation gene. Increased methylation of Cox7A in aged people has shown to be linked with reduced  glucose uptake by skeletal cells

Increased levels of methylation of insulin like growth factor binding proteins-1,7 found in peripheral blood are shown to be linked with increased insulin resistance,

Hence various studies have revealed links between DNA methylation of tissues such as- pancreatic islets, skeleton, liver, adipose, brain, peripheral blood and pathogenesis of Type2 diabetes.

Till now, diabetes medicines, weight loss, healthy diet and exercise serve promising roles in treatment of T2D.

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