Diabetes is a disease that occurs when your blood glucose, also called blood sugar, is too high. Blood glucose is your main source of energy and comes from the food you eat.
A recent study from the Centre for Genomic Regulation (CRG) and Imperial College London found a switch that regulates the activity of a gene that causes diabetes.
The findings highlight potential new vulnerabilities in the disease and could lead to the development of new therapeutic strategies.
HNF1A is a gene that provides instructions for making a protein called hepatocyte nuclear factor-1 alpha.
The protein is expressed in many tissues but is particularly important for the pancreas, where it plays a role in developing beta cells. Beta cells produce the hormone insulin, which regulates blood sugar levels.
Mutations in HNF1A cause cells to create a protein that doesn’t work normally, which in turn affects the function of beta cells.
This results in people developing a disease known as maturity-onset diabetes of the young, where symptoms such as high blood sugar can appear before individuals reach the age of 30.
Though this disease accounts for just 1% of all types of diabetes, it is high in terms of absolute numbers due to the high prevalence of diabetes amongst the worldwide population (5-10%).
HNF1A is also known to play a key role in the susceptibility for the more common form of the disease, type 2 diabetes, in concert with other genetic and non-genetic factors.
Understanding how the HNF1A gene is switched on or off in beta cells could have important implications for understanding why defects in this gene lead to diabetes, or how it could be harnessed to correct the underlying problem.
In the study, the team used a combination of mouse and human models. They focused on an enigmatic part of the genome near HNF1A that has a unique function that has not been described before.
This DNA regulatory element works like as rheostat; if the HNF1A gene transcribes too much it dials it down, if the gene is slacking it dials it back up.
The team says they coined this a stabilizer, in contrast to other DNA regulatory elements such as enhancers, promoters and silencers, and call this particular element HASTER, for HNF1A stabilizer.
The researchers showed that mutations in HASTER cause diabetes in mice.
The study is an example of how studying the non-protein coding sequences in a genome can yield new ways to understand and treat disease.
Just 1-2% of the human genome consists of protein-coding sequences. The remaining ‘dark matter’ is thought to include tens of thousands of regions that regulate gene expression.
By showing that changes to the function of gene regulatory elements such as HASTER can drastically change cell function akin to disrupting the gene itself, the researchers pave the way for future studies that explore the role of non-protein-coding sequences in promoting disease.
The study was conducted by Jorge Ferrer et al and published in Nature Cell Biology.
If you care about diabetes, please read studies that flaxseed oil is more beneficial than fish oil to people with diabetes, and Stanford study finds drug that prevents kidney failure in diabetes.
For more information about diabetes, please see recent studies that blueberries strongly benefit people with metabolic syndrome, and results showing new bandage for foot ulcers in people with diabetes.
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