Discovery of an early predictor of increased diabetes risk

A Montréal research team led by Jennifer Estall at the IRCM discovered that a protein found in muscle tissue may contribute to the development of type 2 diabetes later in life. The study’s results, published in today’s printed edition of the scientific journal American Journal of Physiology - Endocrinology and Metabolism, indicate that the protein could be a promising early predictor of increased diabetes risk.

"My team and I studied PGC-1α, a protein responsible for regulating the production of energy in cells," explains Dr. Estall, Director of the Molecular Mechanisms of Diabetes research unit at the IRCM. "Surprisingly, we found that young mice lacking this protein in their muscle tissue appeared healthier, as they had lower blood sugar levels before and after meals. So, at first, we thought having less of this protein was actually better."

"However, as they aged, the mice lacking the PGC-1α protein developed significant glucose intolerance and insulin resistance, which are hallmarks of type 2 diabetes," adds Dr. Estall. "As a result, we discovered that chronically low levels of this protein in muscle may contribute to the development of diabetes later in life."

While the levels of PGC-1α were only altered in muscle, the scientists observed detrimental effects on the health of other tissues. The study showed that the absence of PGC-1α in muscle increases inflammation in the liver and adipose tissue (fat), revealing a novel link between muscle metabolism and the chronic inflammatory state of the body often associated with metabolic diseases such as type 2 diabetes and cardiovascular disease.

“Our study also suggests that low levels of PGC-1α in muscle could be a promising new way of predicting increased risk of type 2 diabetes at a young age, and drugs to increase the levels of this protein may help prevent or delay the progression of the disease,” concludes Dr. Estall.

According to the Canadian Diabetes Association, more than nine million Canadians are living with diabetes or prediabetes, and 90 per cent of those with diabetes have type 2 diabetes. The Association states that the first step in preventing or delaying the onset of complications associated with diabetes is recognizing the risk factors, signs and symptoms of the disease.

About the research project

The study was conducted in collaboration with Benjamin Haibe-Kains from the IRCM, Jorge L. Ruas from the Karolinska Institutet in Sweden and researchers from the Dana-Farber Cancer Institute in Massachusetts (USA). Jennifer Estall’s team included Sarah Sczelecki (first author), Aurèle Besse-Patin and Alexandra Abboud. Dr. Estall’s research was funded by the Canadian Diabetes Association, the National Research Council of Canada and the IRCM.

About Jennifer Estall

Jennifer Estall obtained her PhD in molecular biology from the University of Toronto. She is Assistant IRCM Research Professor and Director of the Molecular Mechanisms of Diabetes research unit. Dr. Estall is assistant research professor in the Department of Medicine (accreditation in molecular biology) at the Université de Montréal. She is also Adjunct Professor in the Department of Medicine (Division of Experimental Medicine) and the Department of Anatomy and Cell Biology at McGill University. She is a member of the Montreal Diabetes Research Centre (MDRC). Dr. Estall is a Research Scholar from the Fonds de recherche du Québec – Santé and a Research Scholar from the Canada Foundation for Innovation’s Leaders Opportunity Fund. She also holds a New Investigator Award from the Canadian Institutes of Health Research.