Mitochondrial DNA Methylation Gives Clues to Insulin Response in Pre-Diabetics

Diabetes and Mitochondrial DNA Methylation

What if those who are resistant to insulin but don’t have diabetes could help prevent themselves and others from developing the disease? Researchers from Virginia Tech have discovered a biomarker in those who are pre-diabetic that could prevent them and potentially others from getting type 2 diabetes. The researchers uncovered that pre-diabetics, or people who are at high risk of developing type 2 diabetes, who do not respond to insulin had altered DNA in their mitochondria and had an increased amount of DNA methylation in a region that controls the replication of mitochondrial DNA. This possible biomarker has the potential to help prevent the progression of diabetes in those who may be prone to developing it, particularly those who are pre-diabetic.

Former research has uncovered several links between epigenetic mechanisms such as DNA methylation and diabetes. In the current study, published in Clinical Epigenetics, the researchers specifically assessed mitochondrial DNA, DNA methylation, and diabetes.

Forty participants from the diaBEAT-it program who were not diabetic but showed signs of insulin resistance offered their blood for analysis. The long-term diaBEAT-it program is a study headed by several scientists in the Fralin Translational Obesity Research Center. It is made possible by a National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grant.

The researchers found that in the pre-diabetic individuals’ blood, there was a lower amount of mitochondrial DNA and a higher level of methylation compared to healthy individuals. The mitochondrion is an organelle considered to be the “powerhouse” of the cell, converting energy from food into energy able to be utilized by the cells, called adenosine triphosphate (ATP). DNA found in mitochondria is actually circular and it is used by mitochondria for this energy-producing process.

The researchers found that “the reduction of mtDNAn [mitochondrial DNA copy number] in obese human subjects is associated with insulin resistance and may arise from increased D-loop methylation.” The D-loop or displacement loop region of the mitochondrial genome “controls the replication of mtDNA and organization of the mitochondrial nucleoid.” This evidence suggests a newfound process of mitochondrial regulation involving epigenetics and genetics, which could play a role in insulin resistance and the development of diabetes.

“If the body is insulin resistant, or unable to respond properly to insulin, it could affect a person’s mitochondrial function and overall energy levels,” explained Zhiyong Cheng, an assistant professor of human nutrition, foods, and exercise in the College of Agriculture and Life Sciences and a Fralin Life Science Institute affiliate. “Mitochondrial alterations have previously been observed in obese individuals, but this is the first time we’ve made the molecular link between insulin resistance and mitochondrial DNA changes.”

Cheng and his teammate Fabio Almeida, also an assistant professor of human, nutrition, foods, and exercise in the College of Agriculture and Life Sciences and an affiliate of the Fralin Life Science Institute, believe that this connection between insulin resistance and changes in the mitochondrial DNA and DNA methylation could be crucial for treating people who are pre-diabetic and preventing Type 2 diabetes.

The NIDDK states that more than two out of three adults are overweight and greater than one third are actually obese. The obesity epidemic, which has several contributing factors, is mostly due to the overconsumption of energy dense food combined with inadequate or low levels of physical activity. This is not surprising in an environment filled with super-sized soft drinks, prepackaged food and the internet. Yet this practice of consuming more calories than we are able to burn is a contributing factor to many adverse health conditions, including Type 2 diabetes.

“There is no known cure for Type 2 diabetes, and early diagnosis and intervention is critical to prevent this disease,” Almeida said. “Discovery of the biomarker in obese, pre-diabetic individuals advances our understanding of how diabetes develops and provides evidence important for future diagnosis and intervention.”


Source: Louise D. Zheng, Leah E. Linarelli, Longhua Liu, Sarah S. Wall, Mark H. Greenawald, Richard W. Seidel, Paul A. Estabrooks, Fabio A. Almeida, Zhiyong Cheng. (2015). Insulin resistance is associated with epigenetic and genetic regulation of mitochondrial DNA in obese humans. Clinical Epigenetics, 7:60.

Reference: Virginia Tech. Researchers discover link between insulin response and energy producer in pre-diabetic people. 19 Aug 2015. Web.

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About Bailey Kirkpatrick 164 Articles
Bailey Kirkpatrick is a science writer with a background in epigenetics and psychology with a passion for conveying scientific concepts to the wider community. She enjoys speculating about the implications of epigenetics and how it might impact our perception of wellbeing and the development of novel preventative strategies. When she’s not combing through research articles, she also enjoys discovering new foods, taking nighttime strolls, and discussing current events over a barrel-aged sour beer or cold-brewed coffee.


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