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.
"It is a new target," he said.
Dr. 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.
"Agents which increase Sirt3 activity could, therefore, potentially reverse at least some of the adverse effects of type 2 diabetes," the paper concludes.
Co-authors included Enxuan Jing, lead author, as well as Brice Emanuelli, Jeremie Boucher and Kevin Lee, all of Joslin; Matthew D. Hirschey and Eric M. Verdin, both of Gladstone Institute of Virology and Immunology and the University of California, San Francisco; and David Lombard, formerly of the Department of Genetics at Harvard Medical School and currently at the Department of Pathology and Institute of Gerontology at the University of Michigan.
Dr. Verdin noted that by "uncovering the multi-faceted role of SIRT3, we are laying important groundwork to better combat this widespread disease at the cellular level."
|Contact: Jeffrey Bright|
Joslin Diabetes Center