Could diabetes be triggered by a virus?

Alert as scientists identify pathogens that could derail insulin in the body

The exact cause of types 1 and 2 diabetes is not known
Proteins in viruses that mimic insulin may trigger type 1 by tricking the body into thinking the hormone is an invader
Tissues may become resistant to insulin due to the similar viral proteins, causing type 2 diabetes
The Harvard researchers found the insulin-like proteins in four viruses, but think their research could be 'the tip of the iceberg'

Viruses may trigger both type 1 and type 2 diabetes because they contain proteins that mimic insulin, a surprise discovery suggests.

People suffering from both forms of diabetes have shortages of the sugar-metabolizing hormone insulin, but the underlying causes of the disease are largely unknown.

Researchers at Harvard University found that four kinds of viruses produce proteins that mimic insulin, which could lead to diabetes in humans exposed to the microorganisms.

It is not yet clear if humans can get the particular viruses the researchers studied, but the discovery indicates that viruses and other microbes could play a key role in causing diabetes and even other diseases, the researchers say.

Both types of diabetes may be triggered by insulin-like proteins in viruses, a new study found

In type 1 diabetes, which is an autoimmune disease, the body misidentifies its own healthy insulin cells as invaders, and attacks them.

About 30 percent of autoimmune disease are thought to be genetic, while the other 70 percent are believed to be instigated by environmental factors, including toxins, diet and infections.

Type 1 diabetes was once called 'juvenile diabetes,' because its effects often set in during the early stages of life and carry on throughout adulthood.

We know that in this type of the disease, the body destroys the islet cells in the pancreas that produce insulin, a key hormone to the breakdown and use of blood sugar, or glucose for energy.

But we don't know why the immune system turns against these particular kinds of cells.

Previous research has led scientists - including lead study author Dr Emrah Altinidis, a postdoctoral fellow at the Joslin Diabetes Center at Harvard – to hypothesize that the disease could have underlying genetic and viral causes.

'People have had interest in the potential of environmental triggers of diabetes for many years and even some interest in the possibility that viruses could trigger the disease,' says senior study author and chief Academic Officer of the Joslin Center, Dr C Ronald Kahn.

'Up until now, most of that had been focused on that the way they might be causing diabetes might be by causing infection or inflammation in the pancreas,' he says.

The most popular theories have suggested that viruses, including coxsackievirus B4, mumps and rubella, could act as triggers for type 1 diabetes, but still the question of 'how' has remained largely a mystery.

Bacteria and viruses produce proteins, just as our cells do, and Dr Altinidis wondered if some of these proteins might mimic insulin, driving the autoimmune response behind the disease.

To find out whether or not his theory had any merit, Dr Altinidis, with senior study Dr Kahn, had to mine a public database of the DNA sequences of viruses, looking for any section of the genetic code that held instructions similar to those for insulin.

Scientists believe that there are over 300,000 viruses that could affect mammals. Only about 7,500 of those have been sequenced.

THE DIFFERENCE BETWEEN TYPE 1 AND TYPE 2 DIABETES

Both type 1 and type 2 diabetes occur in people whose bodies do not make enough insulin to properly break down carbohydrates into the form of sugar we use for energy, called glucose.

The exact causes of the two forms of the disease are unknown.

Type 1 diabetes, once called 'juvenile diabetes,' is essentially an autoimmune disease that usually begins affecting people in childhood.

The body does not recognize its own insulin, so the immune system attacks it like it would an infection.

Type 2 diabetes is a metabolic disorder in which the body becomes insulin resistant.

In this form, tissues important to metabolizing glucose do not recognize insulin.

Type 2 diabetes usually develops later in life, and may be, in part, a result of a poor diet that exposes the body to too much insulin, leading to resistance. Still, the Harvard researchers found their needle-in-the-haystack - four of them, in fact.

The viruses all belonged to the iridovirus family, which primarily infect fish, including kinds we consume, like grouper.

It is unclear whether or not these viruses infect humans directly, but 'to serve as a trigger for diabetes wouldn't require that they actually infect us,' suggests Dr Kahn, 'if we're just exposed to the proteins that could be enough.'

Their discovery, published in the Proceedings of the National Academy of Sciences, indicates that there 'may be whole different ways viruses can interact with the body and produce hormone-like molecules - in this case, insulin-like - that can could either potentially trigger diabetes for type 1 as an autoimmune disease or cause alterations and mutations by using insulin-like properties, but being weaker than normal insulin,' Dr Kahn explains.

He suspects that when the body detects the insulin-like molecules, it attacks them because they are just dissimilar enough to raise a red flag. But in the process, the immune system may get confused, causing a 'cross-reaction to our own insulin and damage to our own cells.'

He and Dr Altinidis tested the viruses' effects on mouse and human cells. In each kind, they found that the virus proteins caught the attention of some of the same receptors that insulin does, telling them to take up glucose, or blood sugar.

Mice that were injected with the insulin-like viral proteins also had lower blood glucose levels, suggesting that the body had been tricked into thinking there was more insulin present than there actually was.

This could indicate the development of type 2 diabetes as well. The form of the disease that develops later in life involves insulin resistance, meaning that the body produces insulin, but tissues don't respond to it properly, which is a metabolic issue.

Viruses could cause this phenomenon in one of two ways: 'It could cause abnormalities in metabolism itself because they have insulin-like effects, but they are weak, and not fully active,' offers Dr Kahn.

'Or, it could affect the ability of our own cells to respond to our own insulin, a form of insulin resistance,' he says.

The research team's next steps will be to try to use one of the viruses or their proteins to recreate the autoimmune response in type 1 diabetes and to search a large set of human stool samples for evidence of these insulin-like proteins in humans.

Because there are so many viruses, and so many of them are un-sequenced, Dr Kahn says: 'We think this is just the tip of an iceberg in terms of potential' ways that viruses could be implicated in the development of diabetes.