Take This to Heart: TBC1D1 May Help Reduce Risk of Heart Disease in Diabetics
With over 422 million confirmed cases around the world, there’s a good chance that you know someone who suffers from diabetes. Many individuals with type 2 diabetes are also overweight and at increased risk of heart disease. In fact, heart disease is the leading cause of death in type 2 diabetics, which is why researchers have spent decades studying the relationship between heart disease and impaired insulin signaling. Now, a study by Prof. Graham Holloway from the Department of Human Health and Nutritional Sciences has found a strong connection between the absence of a protein involved in glucose regulation and certain heart abnormalities.
TBC1D1 is a protein found in skeletal muscle, which is muscle that can be voluntarily contracted (such as when flexing). The protein is part of a signaling system that helps the body regulate blood glucose levels by responding to insulin and promoting glucose uptake when needed. Recently, TBC1D1 was observed in a different kind of muscle: the heart. What was not clear, however, was how it functioned there. For Holloway, identifying the role of TBC1D1 in the heart was the clear next step in understanding the link between heart disease and diabetes.
“I’ve been interested in studying the relationship between TBC1D1 and insulin resistance for some time,” says Holloway. “Originally, I was focused on the role of TBC1D1 in skeletal muscle metabolism, but from there it seemed obvious to extend our research into the heart.”
Understanding the impact of TBC1D1 on heart disease was no small task, spanning several years and students. Picking up where previous students in the Holloway lab had left off, MSc students Jacy Houad and Pierre-Andre Barbeau bred two groups of rats to advance the project. One group was unchanged, and served as a control. The second group were TBC1D1 genetic “knockouts” which were unable to produce the TBC1D1 protein. As diet is so tightly linked to heart health, the researchers also divided each group of rats into a normal diet (10% fat) subgroup, and a high fat diet (60% fat) subgroup.
After consuming their respective diets for two months, the different groups of rats revealed some interesting differences that hint at a protective role of TBC1D1 against diet-related heart damage. The hearts of rats without TBC1D1 who consumed a high fat diet pumped a lower volume of blood and developed extra fibrous tissue, a condition known as ventricular fibrosis which typically occurs in response to stress or injury. Interestingly, male knockout rats also experienced an abnormal enlargement (known as hypertrophy) of the heart, while female rats did not.
Although it’s too soon to point at TBC1D1 deficiency as a cause for heart disease, Holloway is proud of the massive effort his team has put in over nearly seven years to get to this point.
“This kind of basic science is important to help us better understand not only how heart disease progresses, but what constitutes being ‘healthy’,” says Holloway. “We need to understand how cells respond both in health and unhealthy circumstances so that we can develop interventions to help people who are at risk.”
Holloway next plans to explore if the reason that female rats didn’t have enlarged hearts was due to different hormone levels, or if they simply experience a delay in the onset of hypertrophy. He is also interested in exploring the use of blood flow dynamics to gain a better understanding of heart function beyond echocardiograms.
For now, Holloway encourages the public to not focus solely on the role genes play in their health, but to do what they can every day to maintain a healthy lifestyle.
“More so than looking at the potential for TBC1D1 levels to alter your risk of heart disease, proper diet and exercise is what’s most important,” says Holloway. “Although it is a well-known fact, in reality, people just don’t do it. Even 10 minutes of exercise can reduce your risk of heart disease by 10%. It isn’t as complicated as most people believe. Just do the best you can.”
Other major collaborators for this work include University of Guelph researchers J.S. Huber, S. Paglialunga, L.A. Snook, E.A.F. Herbst, K.M.J.H. Dennis, and J.A. Simpson. Funding for this research was provided by the Natural Sciences and Engineering Research Council of Canada, the Canadian Institutes of Health Research, the Canadian Foundation for Innovation, and the Ontario Research Fund.
Read the full article in the Journal of Physiology.
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