Study explores how exposure to potential triggers can increase risk of type 1 diabetes

A new study has investigated how exposure to certain triggers can increase the risk of type 1 diabetes.

Researchers from The Westmead Institute for Medical Research are looking at an array of potential triggers that could increase the risk of type 1 diabetes. Results of a recent study have shown how exposure to coxsackievirus can increase this risk. Coxsackievirus is a common virus that causes diseases including myocarditis, Hand, Foot and Mouth Disease and gastroenteritis.

The study discovered a key transcription factor (proteins that help turn specific genes on or off) called hypoxia inducible factor 1-alpha (HIF-1A) is behind this increase in risk. Researchers found that mice missing HIF-1A in beta cells (β-cells) had a much higher risk of type 1 diabetes after infection with viruses, including coxsackievirus. Lack of β-cell HIF-1A increased β-cell death and, in turn, increased the incidence of type 1 diabetes.

Lead researcher Professor Jenny Gunton said the findings highlight the key role β-cells play in the risk of diabetes.

If they are healthy, then β-cells recover normally after stresses like viral infections, and diabetes does not develop. But, if β-cells don't cope well with these stresses, it can trigger the immune process that leads to type 1 diabetes.

Our study also showed that the increase in diabetes risk can result from exposure to other stresses, including toxins. So β-cells play a crucial part in preventing their own death when faced with environmental triggers for type 1 diabetes.

We have now identified that HIF-1A is an important factor in this decision about whether the cells recover, or die. This is the first β-cell specific model to show increased risk of type 1 diabetes with a range of triggers."

Professor Jenny Gunton, lead researcher

The findings highlight HIF-1A as a potential pathway for the development of new preventative measures and suggest the possibility that a vaccine for coxsackievirus could help prevent type 1 diabetes in at-risk people.

This comes at a crucial time, as rates of type 1 diabetes are increasing worldwide.

Type 1 diabetes is an autoimmune condition where the immune system attacks and kills β-cells in the pancreas. These are the only cells in the body that make insulin, which we need to control our blood glucose (sugar) levels.

Professor Gunton said:

While there is a strong genetic component to type 1 diabetes, genes alone cannot explain the rising global rates of type 1 diabetes. Currently, the only cures for type 1 diabetes are whole pancreas or islet transplantation, and people have to take insulin for the rest of their lives. So potential preventative strategies are exciting."

Source:

Westmead Institute for Medical Research

Journal reference:

Gunton, J.E. et al. (2019) β Cell Hypoxia-Inducible Factor-1α Is Required for the Prevention of Type 1 Diabetes. Cell Reports. doi.org/10.1016/j.celrep.2019.04.086.

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