New research from the Oklahoma Medical Research Foundation has revealed how diabetes impacts a critical cellular switch in the heart.
These findings, the researchers say, can provide a better understanding of how diabetes affects the heart so that new treatments can be developed to combat the disease.
OMRF’s Kenneth Humphries, Ph.D., and graduate student Lee Bockus worked with biologically engineered mice. Their research focused on a cellular switch called PKA that controls how the heart contracts or pumps blood through the body. In particular, they sought to gain a better understanding of the disease’s specific impact on PKA.
“The heart is literally a pump that works at different workloads depending on what you’re doing,” said Humphries. “If you’re exercising or frightened, your heart beats faster. It’s often called the fight-or-flight response.”
When that response kicks in, your heart speeds up and works harder. PKA is the central switch in the heart that controls this reaction.
Humphries and Bockus discovered that PKA did not work properly in hearts of the diabetic mice. In an effort to compensate for the effects of diabetes, this switch became chronically activated, placing an unnecessary strain on the organ.
“Just like a mechanical pump, when the pump works harder it’s going to use more energy. In the body’s case it would be nutrients as opposed to gasoline or electricity,” said Humphries.
The PKA switch not only strengthens contraction of the heart muscle, it also coordinates its use of energy so that it has enough to meet these increased demands. As a result of this chronic workload, eventually the heart can stop responding.
“This fight-or-flight response is only supposed to happen in acute circumstances, like when you exercise. It’s not meant to be turned on all the time,” said Bockus. “But it happens because PKA is trying to compensate for all the problems in the diabetic heart. Over time, it can lead to clinical problems like heart failure.”
In diabetes, the body has trouble producing or responding to insulin, a hormone that tells cells to take in sugar as a source of energy. Long-term effects of the illness, which affects an estimated 300,000 Oklahomans, include heart disease and other cardiovascular conditions.
“These findings give us a better understanding of how diabetes impacts the heart,” said Humphries. “Using this new information, we can look at developing treatments to control this switch in diabetics.”
The new research appears in The Journal of Biological Chemistry. It was supported by the following grants: P20GM104934 from the National Institute of General Medical Sciences; HR13-183 from the Oklahoma Center for the Advancement of Science and Technology; and 14GRNT20510031 from the American Heart Association.
