July 26, 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 July 26 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.
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. Charles 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."
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- Dan Zhu, Yi Zhang, Patrick P.L. Lam, Subhankar Dolai, Yunfeng Liu, Erica P. Cai, Diana Choi, Stephanie A. Schroer, Youhou Kang, Emma M. Allister, Tairan Qin, Michael B. Wheeler, Cheng-Chun Wang, Wan-Jin Hong, Minna Woo, Herbert Y. Gaisano. Dual Role of VAMP8 in Regulating Insulin Exocytosis and Islet β Cell Growth. Cell Metabolism, 2012; DOI: 10.1016/j.cmet.2012.07.001
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