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Toronto (July 25, 2012) - Scientists at Toronto Western Research Institute have made an important discovery on the role of a SNARE protein known as VAMP8 in the release of insulin from the pancreatic islet beta cells. The study, Dual Role of VAMP8 in Regulating Insulin Exocytosis and Islet β-cell Growth, published today in the journal Cell Metabolism will further our understanding of how the body can produce higher levels of insulin in patients with diabetes.
Dr. Herbert Gaisano, a researcher at the Toronto Western Research Institute, Professor of Medicine and co-director of the Centre for Research in Diet, Digestive Tract and Disease (funded by Canadian Foundation for Innovation and Ontario Ministry of Research and Innovation) at the University of Toronto, shows that VAMP8 is crucial to inducing "newcomer insulin secretory granules" to move to the front of the line and fuse to the plasma membrane, where they are able to release insulin into the bloodstream.
"In patients with diabetes, the granules become lazy, meaning they don't want to fuse to the plasma membrane, which they need to do so in order to release insulin," said Dr. Gaisano, the study's lead author. "Newcomer granules, on the other hand want to reach the plasma membrane and fuse right away – this is why VAMP8 is so important, this protein makes newcomers rush to the front and fuse, and which actually more than compensated for the lazy granules."
This new information also helps to explain how the new class of diabetes drugs that mimic glucagon-like peptide (GLP)-1 works to increase insulin secretion in the body, which Dr. Gaisano's group has found in this study to be acting via VAMP8. With a better understanding of the exact mechanisms that influence GLP-1 drug actions (a major focus of research in Toronto), future drug therapies can be made more effective.
The Gaisano team also revealed a second set of findings while performing this study - the absence of VAMP8 causes more islet beta cell growth, by directly influencing beta cell division i.e. mitosis. This is of importance since beta cells are destroyed in type 1 diabetes (most common type in children) and the latter stages of type 2 diabetes (in adults), and hence inducing an increase in beta cell proliferation would be of great benefit to all diabetic patients.
"The Canadian Institutes of Health Research is pleased to provide support for Dr. Gaisano's research program, which advances knowledge about how diabetes may be effectively managed based on mechanisms that influence GLP-1 drug actions," said Dr. Philip Sherman, Scientific Director of the CIHR Institute of Nutrition, Metabolism and Diabetes.
This discovery in Toronto on a novel mechanism of insulin secretion and beta-cell growth continues the excellence and proud history that started from the discovery of insulin by Banting (Nobel Prize, 1923), Macleod (Nobel Prize, 1923), Collip and Best in Toronto. This underscores the need to sustain the almost century-long support for diabetes research at the most basic science and molecular level. "While insulin and other therapies help people living with diabetes successfully manage the disease for many years, it remains a condition that adversely impacts many organs (heart, kidneys, eyes) of the body causing many health complications," said Dr. Gaisano.
Dr. Mladen Vranic, the last surviving postdoctoral Fellow of Dr. Best, who is now collaborating with the Gaisano team in projects related to pancreatic islets, underscores the importance of this type of research because, "The closer we can get to restoring the body's natural mechanisms for the release of sufficient amount of insulin the better off our patients will be. I believe that this is what Drs. Banting, Macleod, Collip and Best would have intended us to attain."
Toronto Western Hospital has been serving the health care needs of its culturally diverse local community for more than 100 years. Home to the Krembil Neuroscience Centre, one of the largest combined clinical and research neurological facilities in North America, the Toronto Western Hospital is a leader in medical research and also offers expertise in community and population health and musculoskeletal health and arthritis. The Toronto Western Hospital, along with Princess Margaret Hospital, Toronto General Hospital and Toronto Rehabilitation Institute, is a member of the University Health Network and is affiliated with the University of Toronto.
University Health Network consists of Toronto General, Toronto Western and Princess Margaret Hospitals, and Toronto Rehabilitation Institute. The scope of research and complexity of cases at University Health Network has made it a national and international source for discovery, education and patient care. It has the largest hospital-based research program in Canada, with major research in cardiology, transplantation, neurosciences, oncology, surgical innovation, infectious diseases, genomic medicine and rehabilitation medicine. University Health Network is a research hospital affiliated with the University of Toronto.
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