TORONTO RESEARCHERS DISCOVER THE ROLE OF HORMONE RECEPTOR GENE EXPRESSED IN INSULIN-PRODUCING CELLS


(Toronto, October 29, 1996)...Toronto researchers have discovered the function of a hormone receptor gene found on insulin-producing cells, a discovery which clearly links the hormone to diabetes. A team led by Dr. Daniel Drucker, an endocrinologist and researcher at The Toronto Hospital and a member of the University of Toronto's Banting and Best Diabetes Centre, has found that the hormone receptor for GLP-1 - glucagen-like peptide 1 - controls the secretion of insulin.

The discovery is published today in the November issue of Nature Medicine. November is also designated as Diabetes month across Canada. "Our studies have shown that disruption in the function of GLP-1 leads to the development of diabetes," says Dr. Drucker. "This is definitive proof that GLP-1 is necessary for the control of blood glucose levels and insulin secretion." Insulin is found in the pancreas and controls blood sugar, or glucose, levels. The secretion of insulin is controlled by the many receptors and hormones, including the receptor for GLP-1, found on insulin-producing islets cells known as beta cells. To determine the role of GLP-1, the Toronto team studied laboratory mice which were genetically engineered so that they did not produce the receptor for GLP-1. The mice, known as "GLP-1 receptor knock-out mice," all developed diabetes.

Dr. L.A. Scrocchi, a post-doctoral research fellow and a member of Dr. Drucker's team, generated the laboratory mice. "The other receptors and hormones that contribute to beta cell function don't compensate for the GLP-1 receptor mutation," Dr. Drucker explains. "The disruption of GLP-1 signalling results in diabetes. The next step is to look at the development of GLP-1 as an important therapy for people with diabetes."

The same study by Dr. Drucker's team has also shown that GLP-1 is not essential for control of body weight and appetite as suggested in a previous study by a group from the United Kingdom published in January, 1996 in the journal, Nature. "Our studies showed no evidence that GLP-1 is an essential regulator of feeding control and body weight," Dr. Drucker says. "The deletion of GLP-1 receptor in the laboratory mice did not lead to a weight gain nor cause them to eat abnormally," Dr. Drucker says. "Our evidence diminishes the importance of GLP-1 for the central control of feeding that was suggested by the previously published paper." Dr. Drucker's finding comes 75 years after the discovery of insulin at the University of Toronto during 1921-1922, and its first clinical use at the then Toronto General, now The Toronto Hospital, in January, 1922.

The Toronto Hospital and the University of Toronto co-sponsored a three-day international research symposium on diabetes from October 6-9, 1996. Dr. Drucker presented his findings at the symposium which was attended by more than 500 researchers and scientists. Diabetes affects approximately 3 million Canadians.

For more information, contact Josey Panetta, Senior Media Relations Officer, The Toronto Hospital, 416-340-3303