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Genetic “roadblock” hoped to inspire future type 2 diabetes research

October 2, 2007 -- A team of Mount Sinai Hospital researchers has found that a “genetic roadblock” identified in a recent study could pave the way toward novel treatments for type 2 diabetes.

Type 2 Diabetes
Dr. Katrina MacAulay, whose research appeared on the cover of Cell Metabolism

In the study, researchers from the Samuel Lunenfeld Research Institute of Mount Sinai Hospital found the first genetic evidence that the elimination of the gene for glycogen synthase kinase-3a (GSK-3a) in mice sensitizes the animals to insulin.

Insulin is a hormone that helps control sugar (glucose) levels in the blood. In people with type 2 diabetes, the pancreas does not produce enough insulin, or it is not properly used. As a result, sugar accumulates in the blood rather than being absorbed, stored or burned for energy. The study found that by eliminating GSK-3 in mouse models, more sugar became stored in the liver in response to increased insulin sensitivity, indicating that insulin had become more effective.

The study from the laboratory of Dr. Jim Woodgett, Director of the Lunenfeld, and the first scientist to isolate the GSK-3 genes in 1990, made the cover of the October 3 edition of Cell Metabolism.

“We created a ‘genetic roadblock’ by knocking out this particular gene and this made the mice far more efficient in their ability to use insulin to regulate their blood-sugar levels,” said Dr. Woodgett. “Research creates the best medicine and while potential human treatments are likely still years down the road, this study provides strong evidence that chemical inhibitors of this enzyme will be useful for increasing the effective potency of insulin.“

The study was co-authored by Drs. Katrina MacAulay and Bradley Doble. Dr. MacAulay was inspired to become a medical researcher specializing in diabetes because her sister, Ailsa MacAulay, suffers from this disease.

“I hope our findings will inspire other researchers around the world to develop treatments that will reduce symptoms of this epidemic disease as well as its associated complications, such as heart disease, liver disease or limb amputation,” said Dr. MacAulay.

Currently, more than two million people in Canada suffer from diabetes. It is one of the fastest growing diseases in the country with more than 60,000 new cases diagnosed each year.

Type 2 diabetes makes up about 90 per cent of all cases, with most evidence suggesting that it could be prevented or delayed by maintaining a healthy lifestyle.

“With this research, another piece in the puzzle has been put in place. It advances our understanding of how the complex mechanisms activated by insulin work. Understanding the details of this picture is central to developing new drugs that can help people with diabetes control their blood sugar,” says Dr. Diane T. Finegood, Scientific Director of the CIHR-Institute of Nutrition, Metabolism and Diabetes.

The health-care costs associated with diabetes are estimated at more than $1.6 billion by the Public Health Agency of Canada. This study was supported by funding from the Banting and Best Diabetes Centre and the Canadian Institutes of Health Research.

About the Samuel Lunenfeld Research Institute of Mount Sinai Hospital
The Samuel Lunenfeld Research Institute is a recognized leader in the world’s research community, with a reputation for top-quality investigators and scientific excellence. It has an extensive impact on scientific advancement and is home to many of Canada’s outstanding biomedical researchers.

About Mount Sinai Hospital

Mount Sinai Hospital is an internationally recognized academic health centre affiliated with the University of Toronto. It is known for excellence in the provision of compassionate patient care, innovative education and world-leading research. Our Centres of Excellence are Women’s and Infants’ Health; Surgery and Oncology; Acute and Chronic Medicine; Laboratory Medicine and Infection Control; and the Samuel Lunenfeld Research Institute. Mount Sinai Hospital brings together Bright Minds and Big Hearts to provide The Best Medicine.

About the Canadian Institutes of Health Research
The Canadian Institutes of Health Research (CIHR) is the Government of Canada’s agency for health research. CIHR’s mission is to create new scientific knowledge and to catalyze its translation into improved health, more effective health services and products, and a strengthened Canadian health-care system. Composed of 13 Institutes, CIHR provides leadership and support to more than 11,000 health researchers and trainees across Canada.

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For more information, please contact:

Noemie Wiggett
Communications and Marketing
Mount Sinai Hospital