Scientists showed that the enzyme, Sirt3, is decreased in the skeletal muscle of humans and animals with diabetes by at least half, compared to those without diabetes and that this may contribute to development of insulin resistance, one of the earliest manifestations of the disease. Sirt3 is found in the mitochondria, the power producers of cells that convert energy into usable forms.
"Ours is perhaps the first study to understand what is going wrong in the mitochondria of those with diabetes," said senior author C. Ronald Kahn. "Many studies have shown that the mitochondria don't work well in those with diabetes. This points to a cause of why they don't work well."
Doctor Kahn said the study sought to look at how decreased Sirt3 levels might affect the metabolism of cells, particularly how it could affect insulin action in cells. "We know that one of the hallmarks of early diabetes is insulin resistance in muscle, but we didn't know what caused it," he said.
He said the study showed that when Sirt3 levels are low, as they are in the case of diabetes, the mitochondria of the cells are not as efficient in energy metabolism as they should be.
When the mitochondria become inefficient, they generate what are known as reactive oxygen species (ROS), chemically reactive molecules containing oxygen, which create insulin resistance in the muscles, he said. "This is the first time this has been shown," added Kahn.
The goal for the future will be to find ways to restore levels of Sirt3 or increase the activity of the existing Sirt3, perhaps with a drug, in a bid to improve insulin resistance in the muscle and improve muscle metabolism, he said.
Kahn noted that this study is one of the first demonstrations of a single defect that could affect mitochondrial metabolism and insulin signaling in the muscle. "In further studies we will try to understand what proteins Sirt3 acts on," he said.
He noted that one of the earliest hallmarks of diabetes is insulin resistance in the skeletal muscle. As a result, a drug to boost Sirt3 levels could be useful in the treatment of prediabetes or in those newly diagnosed with the disease, he said.
MEDICA.de; Source: Joslin Diabetes Center