Researchers at West Virginia University want to know why people with Type 2 diabetes commonly develop heart disease, a major cause of death among this population.
To understand why the system that carries proteins needed to fuel the heart dysfunctions in people with Type 2 diabetes, scientists will use diabetic animal models to examine the part of cells — the mitochondria — that generates the primary energy source for fueling all the heart’s activities.
A four-year study, led by John Hollander, professor and senior assistant dean for Research and Graduate Education in the WVU School of Medicine Department of Human Performance, is funded by a more than $2 million grant from the National Heart, Lung and Blood Institute.
“It’s a hugely important issue as it relates to our local Appalachian population where diabetes rates are one of the worst in the country,” Hollander said. “Diabetic patients tend to either die of or have a complication related to the cardiovascular system, including the heart.”
While statistics vary as new cases are reported, West Virginia typically ranks in the No. 1 or No. 2 spot in the United States. The American Diabetes Association reported in March that 15.7% of West Virginia adults have diagnosed diabetes. Additionally, 34.8% of the state’s adult population have prediabetes and around 45,000 West Virginians are estimated to have diabetes and don’t know it.
“Since the heart is constantly beating, constantly contracting, it’s a large consumer of energy and, as an organ, it’s one of the larger consumers of energy,” Hollander said.
In non-diabetic patients, proteins necessary for energy production to keep the heart functioning are naturally imported from the cell’s nucleus to the mitochondria. However, Hollander said that for people with Type 2 diabetes, something goes awry.
“There are losses of proteins overall and an ineffectiveness of this import system,” Hollander said. “We want to understand what makes this process less efficient for a diabetic heart patient. By using animal models, we’ll manipulate certain proteins we think are important in this process. That can help us understand if there are things we can do to help fix this system.”
Researchers will also approach the process from an additional perspective. Focusing on the fact that the protein import process in the mitochondria is faulty and has a negative impact on the mitochondria, they’ll explore whether a similar negative reaction occurs outside of the mitochondria.
“When these proteins are not getting into the mitochondria, it’s like when you’re in a traffic jam and everything is backed up,” Hollander explained. “This causes stress, but does it elicit some sort of stress outside of the mitochondria?”
Hollander will be assisted in the study by Venkatesh Sundararajan, associate professor in physiology, pharmacology and toxicology; and David Smith, professor in biochemistry and molecular medicine.
Preliminary data was collected through Hollander’s previous studies funded by the Community Foundation for the Ohio Valley – Whipkey Trust.
“The Community Foundation for the Ohio Valley – Whipkey Trust has been a key partner for our laboratory and many others at WVU trying to come up with cures for our diabetic population,” Hollander said. “Their contributions have been critical, and they are a great example of collaboration between WVU and the community.”
Hollander will also collaborate with the WVU Heart and Vascular Institute to gain clinical insight.
“Hopefully, we’ll have some really interesting findings that allow us to continue to propose new aims that build on our results,” Hollander said. “We are a land-grant institution and I take that part seriously as it relates to research that can at some point benefit folks in our state.”
Editor’s note: The use of animals in this project was evaluated by the WVU Institutional Animal Care and Use Ethics Committee. WVU is voluntarily accredited by AAALAC, a national peer organization that establishes a global benchmark for animal well-being in science.
