For more than a decade, Oklahoma Medical Research Foundation scientist Ken Humphries, Ph.D., has investigated why the heart becomes so vulnerable in diabetes and other metabolic diseases.
Now, Humphries’ research team at OMRF has identified a likely culprit: a protein that regulates the heart’s system for processing sugar. The discovery points the way toward a potential therapeutic target for diabetic heart disease, a condition that affects millions of Americans.
Working with experimental mice in Humphries’ lab, graduate student Kylene Harold first found that when the rodents lacked a protein called PFKFB2, their hearts became enlarged, pumped blood less efficiently, and were at greater risk for dangerous arrhythmias. In new studies, Harold and Humphries have discovered that reversing certain metabolic changes protected the heart from these arrhythmias when PFKFB2 is lost.
“We learned from these studies that the protein acts like a gate to help the heart process sugar efficiently,” Harold said. “When it becomes impaired, the gate becomes stuck, and sugar spills over into alternate pathways. Over time this leads to heart disease.”
Importantly, this seems to occur only in conjunction with metabolic disease. “So, we can predict with some certainty that if you have uncontrolled diabetes, your heart cells probably have low levels of this protein,” Humphries said.
Humphries said humans with diabetes have reduced levels of PFKFB2 in their hearts. So now the research focus becomes how to either increase PFKFB2 or develop a drug that keeps the remaining protein more active.
This discovery was published in Circulation: Arrhythmia and Electrophysiology, a journal of the American Heart Association.
The studies were supported by the following National Institutes of Health grants:
- R01HL160955 and F31HL176095 from the National Heart Lung and Blood Institute
- R24GM137786 and P20GM103447 from the National Institute of General Medical Sciences
- F31AG079620, P20GM139763 and P30AG050911 from the National Institute on Aging
- R01NS135830 from the National Institute of Neurological Disorders and Stroke
The work was also supported by grant No. 20SRG35490443 from the American Heart Association and a grant from the Presbyterian Health Foundation.
This content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
