Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

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

23.08.2011
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."

The study was supported by research grants to Kahn and Verdin as well as a grant from the Ellison Foundation and the Mary K. Iacocca Professorship. The study also received support from the Joslin DERC cores laboratories.

Jeffrey Bright | EurekAlert!
Further information:
http://www.joslin.org

More articles from Health and Medicine:

nachricht Investigators may unlock mystery of how staph cells dodge the body's immune system
22.09.2017 | Cedars-Sinai Medical Center

nachricht Monitoring the heart's mitochondria to predict cardiac arrest?
21.09.2017 | Boston Children's Hospital

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>