Researchers discover potential treatment for diabetes-related heart damage

Researchers from Johns Hopkins University successfully restored normal heart function in diabetic rats.
The study was the first to identify a key aspect of diabetes-related heart damage. Developed further, it could lead to new treatments for the condition.
It has long been understood that the hearts of people with diabetes are unusual in several ways: they conduct electric signals improperly and their regular contractions are dysfunctional. Previous research has suggested that these abnormalities are due to an inability to respond properly to calcium, which is responsible for triggering the contractions of muscles.
So far, it hasn’t been clear why. “Glucose toxicity in the heart is one of the gravest complications of diabetes and one whose mechanisms are poorly understood,” said Genaro Ramirez-Correa, lead investigator of the study and instructor of paediatric cardiology at the Johns Hopkins Children’s Centre and member of the Johns Hopkins Innovative Proteomics Centre in Heart Failure.
This study aimed to find out why people with diabetes do not react properly to calcium. The team of researchers found a sugar molecule and an enzyme that could be responsible.
The molecule, known O-GIcNAc, and the enzymen, known as OGT, are moved around cells until they end up in the wrong place. Once there, they disrupt the function of proteins that control the contraction of muscles.
First, the team found that O-GIcNAc levels are much higher in rats with diabetes than healthy rats. The, using a laser microscope, the researchers examined the inside of heart cells that control muscle contraction. They discovered that O-GIcNAc and OGT drift over to the middle of the cell, where the most important parts of the muscle contractions process take place. The effect is disruptive.
“When the sugar molecule and the enzyme move into the control centre of muscle contraction, it’s like putting a drop of molasses inside a Swiss watch. You end up disrupting a perfectly synchronised mechanism,” said Ramirez-Correa.
In most people without diabetes, calcium flows into heart cells, which encourages muscle proteins to initiate contraction. But with O-GIcNAc and OGT drifting into the middle of the cell, the proteins cannot make the connections they need to make. As a result, muscle contraction in the hearts of people with diabetes functions improperly.
The research is in a preliminary stage, but if developed further it could have significant therapeutic potential. It could perhaps even lead to effective treatments for many cases of diabetes-related heart disease.
“Our research maps out the molecular chain of events inside the cells that is responsible for the heart muscle damage seen in diabetes.”
“We know that amino acids – the building blocks of proteins – leak into the blood when heart proteins break down. When sugar molecules latch onto the heart’s contractile proteins, the amino acids they release could serve as telltale footprints that signal glucose toxicity in a single blood drop from a patient with diabetes.”
The research was published in Diabetes.