Decreased Mitochondrial Enzyme Activity Linked to Type II Diabetes

A malfunctioning enzyme in the mitochondria of smooth muscle cells has been identified as early precursor of type II diabetes.

The enzyme is SIRT3 or sirtuin (silent mating type information regulation 2 homolog) 3, which is the third member of the mammalian sirtuin family. The SIRT3 gene encodes a protein, (SIRT3), which exhibits NAD+-dependent deacetylase activity.

In a recent study, investigators at the Joslin Diabetes Center (Boston, MA, USA) explained how their search for the molecular basis of insulin resistance in smooth muscle cells led them to SIRT3. They reported in the August 30, 2011, issue of the journal Proceedings of the [US] National Academy of Sciences that Sirt3 was decreased in the skeletal muscle of humans and animals with diabetes by at least half, compared to those without diabetes and that reduced SRT3 activity seemed to contribute to development of insulin resistance.

They found that in mice genetically engineered to lack the SRT3 gene, the absence of this enzymatic activity impaired mitochondrial efficiency, which led to the generation of reactive oxygen species (ROS) and the development of insulin resistance.

“We know that one of the hallmarks of early diabetes is insulin resistance in muscle, but we did not know what caused it,” said senior author Dr. C. Ronald Kahn, professor of medicine at Harvard University’s Joslin Diabetes Center. “Ours is perhaps the first study to understand what is going wrong in the mitochondria of those with diabetes. Many studies have shown that the mitochondria do not work well in those with diabetes. These results point to a cause of why they do not work well.”

“Agents which increase Sirt3 activity could, therefore, potentially reverse at least some of the adverse effects of type 2 diabetes,” said Dr. Kahn.

Related Links:
Joslin Diabetes Center