The research suggests that glucose 6-phosphate (G6P) - a breakdown product of glucose - causes direct stress to the heart by altering muscle proteins and pump functioning that can lead to heart failure.
Writing in the Journal of the American Heart Association, the US-based researchers noted that high consumption of starchy and sugary foods can lead to an accumulation of G6P that adds to the already damaging effects of a sugar-rich diet.
"When the heart muscle is already stressed from high blood pressure or other diseases, and then takes in too much glucose, it adds insult to injury," said Professor Heinrich Taegtmeyer from the University of Texas Health Science Center at Houston.
"We propose that glucose metabolic changes precede and regulate functional (and possibly also structural) remodelling of the heart," the authors explained.
Taegtmeyer and colleagues subjected the working rat heart ex vivo to a high workload in the presence of different energy‐providing substrates including glucose, glucose analogues, and non-carbohydrate substrates.
"We observed an association between G6P accumulation, mTOR activation, endoplasmic reticulum (ER) stress, and impaired contractile function, all of which were prevented by pre-treating animals with rapamycin (mTOR inhibition) or metformin (AMPK activation)," they explained.
After this observation the team then tested whether the same observations held up in live rats (in vivo) - finding enhanced glucose tracer analogue uptake and contractile dysfunction preceding dilatation of the left ventricle.
"Finally, we examined failing human hearts and found that mechanical unloading decreased G6P levels and ER stress markers," said the authors. "We implicate a critical role for G6P in load‐induced mTOR activation and ER stress."