Unlike your skeletal muscles, your heart doesn’t fatigue, and it requires a constant energy supply. Usually that energy source is fat, but if fat isn’t available, the heart settles for glucose.
This energy-selection process, known as metabolic flexibility, sometimes becomes impossible due to diabetes or aging. Oklahoma Medical Research Foundation scientist Kenneth Humphries, Ph.D., recently received two National Institutes of Health grants totaling $2.2 million to investigate potential solutions for this disorder.
The goal behind the research the grants fund is to develop treatments that restore metabolic flexibility and increase “healthspan” – the period of life in which someone enjoys relatively good health.
Humphries will examine a complication of diabetes called diabetic cardiomyopathy through a four-year, $1.7 million grant from the National Heart, Lung, and Blood Institute.
“For most people, the heart’s metabolism relies upon fat, but after a big spaghetti dinner, it will start burning the glucose, which is sugar,” Humphries said. “If you have diabetes, the heart’s metabolism can’t make that switch. It remains locked on using the fat, which ultimately causes diabetic cardiomyopathy.”
In people with this condition, the heart begins to lose its normal pumping function. It can lead to irreversible heart failure. Several drugs can help people with diabetes use the body’s sugar more efficiently, but none exist specifically to do so in the heart, Humphries said.
“What’s troubling is that cardiomyopathy can occur even in people who are doing a great job of managing their diabetes,” Humphries said.
His lab will try to expound upon a discovery made in 2019 by OMRF scientist Maria Newhardt, Ph.D., who was then a graduate student in Humphries’ lab. “What we hope to show is that if you had a drug that can improve cardiac metabolism, it would actually improve your diabetes,” Humphries said.
Separately, a new, two-year, $480,700 grant from the National Institute on Aging is funding Humphries’ research into age-related changes in heart metabolism.
Humphries will work with fellow OMRF scientists Benjamin Miller, Ph.D., and Mike Kinter, Ph.D., to explore why mitochondria, often called the powerhouse of the cell, decline with age, leading to a loss of heart function. Their research will focus on a particular enzyme that decreases as we age.
“Competition for these kinds of federal dollars is intense. To be awarded two grants in close proximity is an impressive feat,” said Holly Van Remmen, Ph.D., chair of OMRF’s Aging and Metabolism Research Program. “Dr. Humphries is making significant progress toward treatments for health problems that impact millions of Americans. These grants will fund research that propel us toward those eventual treatments.”
The National Heart, Lung, and Blood Institute grant is R01HL160955-01A1. The National Institute on Aging grant is R21AG073745-01A1. Both are part of the NIH.