Navigation Links
Joslin researchers identify new target for treatment of type 2 diabetes and prediabetes

BOSTON -- Aug. 22, 2011 -- Researchers at the Joslin Diabetes Center have shown that an enzyme found in the mitochondria of cells is decreased in the skeletal muscle of those with diabetes, a finding that could lead to the development of drugs to boost the activity of this enzyme in an effort to fight the disease.

A paper in published online today in the Proceedings of the National Academy of Sciences, 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, M.D., Head of the Joslin Section on Integrative Physiology and Metabolism and the Mary K. Iacocca Professor of Medicine at Harvard Medical School. "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."

Dr. 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," Dr. Kahn said.

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

Related biology news :

1. Joslin research finds nearly three-quarters of youths with diabetes insufficient in vitamin D
2. NC State researchers get to root of parasite genome
3. Researchers find animal with ability to survive climate change
4. Researchers find an essential gene for forming ears of corn
5. Researchers note differences between people and animals on calorie restriction
6. Researchers study acoustic communication in deep-sea fish
7. Researchers discover that growing up too fast may mean dying young in honey bees
8. Researchers study how pistachios may improve heart health
9. UI researchers find potentially toxic substance present in Chicago air
10. Researchers develop new self-training gene prediction program for fungi
11. Case Western Reserve University researchers track Chernobyl fallout
Post Your Comments:
Related Image:
Joslin researchers identify new target for treatment of type 2 diabetes and prediabetes
(Date:11/20/2015)... 20, 2015 NXTD ) ("NXT-ID" ... the growing mobile commerce market and creator of the ... , was recently interviewed on The RedChip Money ... this weekend on Bloomberg Europe , Bloomberg Asia, ... --> NXTD ) ("NXT-ID" or the "Company"), a ...
(Date:11/19/2015)... Calif. , Nov. 19, 2015  Based on ... Frost & Sullivan recognizes BIO-key with the 2015 Global ... Each year, Frost & Sullivan presents this award to ... line catering to the needs of the market it ... product line meets and expands on customer base demands, ...
(Date:11/19/2015)... -- Although some 350 companies are actively involved in molecular ... according to Kalorama Information. These include Roche Diagnostics, Hologic, Abbott ... of the 6.1 billion-dollar molecular testing market, according to ... Diagnostic s .    ... one company and only a handful of companies can ...
Breaking Biology News(10 mins):
(Date:11/25/2015)... --> ... 2020 report analyzes that automating biobanking workflow will ... long-term samples, minimizing manual errors, improving the workflow ... errors such as mislabeling or inaccurate sample barcoding ... a vital role in blood fractionation, DNA extraction, ...
(Date:11/25/2015)... 25, 2015  PharmAthene, Inc. (NYSE MKT: PIP) announced ... stockholder rights plan (Rights Plan) in an effort to ... (NOLs) under Section 382 of the Internal Revenue Code ... PharmAthene,s use of its NOLs could be substantially limited ... in Section 382 of the Code. In general, an ...
(Date:11/25/2015)... 2 nouvelles études permettent d , ... les souches bactériennes retrouvées dans la plaque dentaire ... . Ces recherches  ouvrent une nouvelle voie ... de l,un des problèmes de santé les plus ... --> 2 nouvelles études permettent d , ...
(Date:11/25/2015)... Studies reveal the differences in species of bacteria ... for more effective treatment for one of the most commonly ... --> --> Gum disease is one ... relatively little was understood about the bacteria associated with it ... researchers from the WALTHAM Centre for Pet Nutrition together with ...
Breaking Biology Technology: