Discovery of novel function of hormone found in gut that may lower glucose levels in diabetes

A research team led by Dr. Tony Lam at the Toronto General Research Institute and the University of Toronto discovered a novel function of a hormone found in the gut that might potentially lower glucose levels in diabetes.

In this ground-breaking study on a rat model, Dr. Lam's team discovered that activating receptors of the cholecystokinin (CCK) peptide hormone in the gut rapidly and potently lowers blood glucose levels by triggering a signal to the brain and then to the liver to lower glucose or sugar production. In the same experiment, CCK failed to lower blood glucose in rodents fed a high-fat diet for three days.

The research is published as the cover story in the August issue of the internationally prestigious journal Cell Metabolism. The paper is entitled, "Intestinal Cholecystokinin controls Glucose Production through a Neuronal Network".

"Our findings reveal a novel role for the CCK hormone and suggest that CCK-resistance in the gut may contribute to high blood sugar levels in response to high-fat feeding in rodents. Understanding how to overcome CCK-resistance in the gut so that blood sugars can be lowered could be a novel therapeutic approach to diabetes and obesity," says Dr. Lam, who holds the John Kitson McIvor (1915 - 1942) Chair in Diabetes Research at the Toronto General Research Institute and University of Toronto and is Assistant Professor in the Departments of Physiology and Medicine at the University of Toronto. "This paper compliments our study that was published last year in Nature indicating that in the future, we may be able to design a drug to target the gut to lower glucose levels in patients with diabetes."

Dr. Lam stressed that the clinical therapeutic implications of the current findings remain largely unknown. A large amount of time will be required to determine whether enhancing CCK action in the gut of humans is effective and safe in lowering glucose levels in healthy individuals as well as patients with diabetes and obesity. Many laboratories around the world are in a race to find alternatives ways in which to lower glucose levels because of the severe complications which can result from high sugar levels. Currently, those with diabetes lower their glucose through diet, exercise, anti-diabetic tablets or insulin injections.

"Diabetes is a growing epidemic in our society, and finding better ways to prevent and treat it is a research priority at the Canadian Institutes of Health Research (CIHR)," noted Dr. Philip Sherman, Scientific Director of CIHR's Institute of Nutrition, Metabolism and Diabetes. "We are very impressed with Dr. Lam's findings. His work is an important contribution to the search for better treatments to reduce glucose levels for those living with the disease."

"Dr. Lam is a rising star in the field of diabetes research. His pioneering research continues to identify the importance of the intestine and brain in regulating blood glucose. This exciting research opens up new possibilities for therapy," said Dr. Stephen Matthews, Ernest B. and Leonard B. Smith Professor and Chair Department of Physiology, University of Toronto.

Other researchers involved in the study include Grace Cheung, Andrea Kokorovic, Carol Lam and Madhu Chari from the graduate Department of Physiology at the University of Toronto and the Toronto General Research Institute.

The work was funded by the Canadian Institutes of Health Research.

Diabetes Facts:

• More than two million Canadians have diabetes and that number is expected to increase to three million by 2010
• A North American child born in 2000 has a one in three chance of being diagnosed with diabetes in his or her lifetime
• Diabetes is a contributing factor in the deaths of approximately 41,500 Canadians each year; Canadian adults with diabetes are twice as likely to die prematurely, compared to people without diabetes
• Life expectancy for people with diabetes may be shortened by 5 to 15 years
• By 2010, it is estimated that diabetes will cost the Canadian healthcare system $15.6 billion a year, and that number will rise to $19.2 billion by 2020
• A person with diabetes can be faced with medication and supply costs up to $15,000 a year