Research Profile - Canadian Inspiration
A Laval researcher, inspired by the work of Banting and Best, provides insight into how insulin resistance develops.
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Dr. André Marette
Health researchers can be drawn to their work for a variety of reasons. Some have personal experience with the disease that they are studying. In other cases, influential mentors steer young researchers towards a particular field. But Dr. André Marette's inspiration to study diabetes traces back to Frederick Banting and Charles Best – two of the most iconic figures in Canadian health research.
As a PhD student studying metabolic pathways, Dr. Marette read The Discovery of Insulin. This compelling account of Banting and Best's landmark research, written by historian Michael Bliss, was a great inspiration to the young researcher.
"Reading about how these guys achieved the discovery through collaboration was one of the reasons I decided to study diabetes," says Dr. Marette.
Diabetes is a disturbance in the way the body normally produces or responds to the hormone insulin.
Insulin is secreted by the pancreas, and it tells the body to absorb and "burn" glucose (sugar) in the blood. When the body becomes desensitized to this signal, the pancreas boosts insulin production. This condition, known as insulin resistance, is a major risk factor for type 2 diabetes and cardiovascular disease. When the pancreas can't keep up with the increased demand for insulin, blood sugar levels start to rise and can lead to diabetes.
Researchers don't fully understand the underlying causes of insulin resistance. Too much sugar and fat and not enough exercise are strong risk factors, but they do not act alone to cause the disease.
"I think the most important thing to realize [about the causes of insulin resistance] is that it's probably a combination of two distinct but interacting factors: genetic susceptibility combined with a poor lifestyle," says Dr. Marette.
With support from the Canadian Institutes of Health Research (CIHR), Dr. Marette and his team are taking a closer look at the mechanisms behind insulin resistance. They are currently focusing on two important biochemical pathways (series of chemical reactions in the body): one involved with nutrient sensing and another that triggers inflammation. Dysfunction in either of these pathways could interfere with the body's ability to regulate blood sugar.
Dr. Marette's ultimate goal is to find novel treatments and approaches that will help address insulin resistance before it develops into a more serious health problem.
"What is clear with insulin resistance is that the sooner you can alleviate it or reduce it, the better your chance of not developing type 2 diabetes," says Dr. Marette.
Dr. Marette's research has already identified potential treatments. His team found that omega-3 fatty acids can inhibit the inflammatory pathways that contribute to insulin resistance. They've also identified fish proteins that reduce insulin resistance in animal models and have shown promise in humans. In addition, they are looking for new molecules isolated from plants that have anti-diabetic effects.
"There are already examples of [diabetes] drugs on the market that are derived from plant molecules. So we're trying to find out if Mother Nature has other secrets that we could use to treat these metabolic syndromes," says Dr. Marette.
Insulin at 90
The discovery of insulin saved an untold number of lives. It made it possible for people with diabetes to live with their disease. But 90 years later, there are still challenges to address. Dr. Marette feels that there are several key areas where we still have much to learn:
- "When I started as a student, we used to say 'How insulin works is a black box.' That was maybe 20, 25 years ago. Now the black box is not black anymore, but it's still grey."
- "We need to identify the genes that increase the risk for insulin resistance."
- "We need to better integrate the information we have about the molecular pathways that are behind the development of insulin resistance," says Dr. Marette. "The more we know about the metabolites that are involved, the better we can target our drugs or our different compounds to treat the disease."
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