Muscle protein linked to diabetes risk

Millions of Canadians live with type II diabetes and the number grows exponentially each year. While the current statistics surrounding diabetes aren’t very positive, a new scientific discovery may just have the potential to change the way the disease is treated and prevented in the future.

A team of researchers from the Institut de Recherches Cliniques de Montreal (IRCM) have identified a protein found in muscle tissue that could be a new way of predicting an early risk of type II diabetes.

The protein is called PGC-1α and it is responsible for the regulation of energy production in cells.

The findings of the study, published in the American Journal of Physiology – Endocrinology and Metabolism in January 2014, revealed that young mice lacking the protein developed significant glucose intolerance and insulin resistance as they aged, which are key markers of type II diabetes.

Researchers at Harvard were the first to study the protein PGC-1α in relation to diabetes. Published in the journal Nature in September 2001, the earlier study concluded that the protein was a key modulator in a process in the liver called gluconeogenesis, which is a mechanism used by the body to keep blood glucose levels at optimum levels. The process is a key target for type II diabetes therapy.

The study showed that the absence of the PCG-1a protein in the muscle tissue was correlated with increased inflammation and fatty tissue in the liver.

“There’s a lot of interest right now in understanding how muscle biology affects diabetes because there is strong evidence that when you exercise, you decrease your risk of getting diabetes,” said Dr. Jennifer Estall, director of the research unit on the molecular mechanisms of diabetes at the IRCM, in a phone interview.

Additionally, even though the levels of PGC-1α have only been modified in muscle, the scientists observed negative health effects in other tissues. The study showed that the absence of the PGC-1α protein in the muscle increased inflammation and fatty tissue in the liver. This shows a new link between muscle metabolism and chronic inflammation, which is frequently associated with metabolic diseases such as type II diabetes.

Dr. Estall concluded that low levels of PGC-1α in muscle could ultimately be a way to predict early risk of type 2 diabetes and that medications that increase levels of this protein could help prevent or delay disease progression.

“These findings from Dr. Estall have shown, again, a link between PGC-1α and healthy energy metabolism in tissues. It reinforces the importance of this protein in protection from type II diabetes,” confirmed Dr. Mary-Ellen Harper, a professor of biochemistry in the Faculty of Medicine at the University of Ottawa, in a phone interview.

The results of the study are especially positive considering the state of diabetes in Canada. According to the Canadian Diabetes Association, more than 9 million Canadians live with diabetes or prediabetes – a condition that, if left unchecked, puts the person at risk of developing type II diabetes. This means that nearly 1 in 4 Canadians either has diabetes or prediabetes. It is estimated that there are nearly 1.4 million people diagnosed with diabetes in Ontario alone (9.4 per cent of the population), and this will rise to nearly 2 million (11.9 per cent of the population) by 2020. Canada’s aging population, rising obesity rates, and increasingly sedentary lifestyle are just some of the contributing factors to the dramatic rise of the disease.

However, while the potential application of this protein in the detection and treatment of type II diabetes sounds promising, it is also far from becoming a reality in the near future.

Dr. Estall says it would take about 15 to 20 years for the protein to start being used in clinical drug trials. But according to Dr. Estall, one of the important things the protein does now is change the mindset around type II diabetes.

Type II diabetes is a disease in which the pancreas does not produce enough insulin, or the body does not properly use the insulin it makes. As a result, glucose, or sugar, builds up in the bloodstream instead of being used for energy. People get glucose from foods with carbohydrates like bread, potatoes, rice, pasta, milk and fruit. The body needs the hormone insulin in order to use glucose properly, as it helps the body to control the levels of glucose in the blood.

Type II diabetes is considered preventable as many of the major risk factors are conditions that can be reversed, such as having high blood pressure, high cholesterol, or being overweight.

‘There is kind of a negative stigma towards diabetes because a lot of the general public, and even scientists believe that it’s a lifestyle disease.’ — Jennifer Estall

Recently, several provinces have made large significant commitments to the fight against diabetes in Canada. Earlier this year, the Government of Ontario announced a nearly $10 million investment to support local communities and health professionals in their efforts to prevent type II diabetes. In Saskatchewan, Lions clubs plan to hold 50 or more diabetes screening and education events across the province over the next two years. However, these investments are largely focused on diabetes detection and education, as opposed to financing research.

Dr. Estall says that altering how type II diabetes is understood would help further support the research which is already underway. Dr. Estall says there is active research attempting to identify chemicals that might induce the protein PGC-1α in muscle.

“What’s interesting about our study is that our mice were not fat and they were not given any kind of diet to induce diabetes,” said Dr. Estall. “All that we did was create a genetic mutation in them that would mimic something that has been seen in humans. We are actually showing that some of these genetic problems in humans, something that you can’t affect through lifestyle decisions, can put you at higher risk for diabetes.”

Story produced by Hilary Thomson