Researchers identify new target for treatment of type 2 diabetes and prediabetes

August 22, 2011 in Medical research

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 , showed that the enzyme, Sirt3, is decreased in the skeletal muscle of humans and animals with by at least half, compared to those without diabetes and that this may contribute to development of , one of the earliest manifestations of the disease. Sirt3 is found in the , 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 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 as they should be.

When the mitochondria become inefficient, they generate what are known as reactive (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 . 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."

Provided by Joslin Diabetes Center

4 /5 (4 votes)  

Filter


Move the slider to adjust rank threshold, so that you can hide some of the comments.


Display comments: newest first

Ricochet
Aug 23, 2011

Rank: not rated yet
Since this will lead to more drugs on the market, I hope the BBDCs (Big Bad Drug Companies) won't bury this.
Rank 4 /5 (4 votes)
Relevant PhysicsForums posts

More news stories

Study reveals new mechanism for estrogen suppression of liver lipid synthesis

By discovering the new mechanism by which estrogen suppresses lipid synthesis in the liver, UC Irvine endocrinologists have revealed a potential new approach toward treating certain liver diseases.

Medical research created May 23, 2013 | popularity 5 / 5 (1) | comments 0 | with audio podcast

MRI-based measurement helps predict vascular disease in the brain

Aortic arch pulse wave velocity, a measure of arterial stiffness, is a strong independent predictor of disease of the vessels that supply blood to the brain, according to a new study published in the June issue the journal ...

Medical research created May 23, 2013 | popularity not rated yet | comments 0

Antibiotics: A new understanding of sulfonamide nervous system side effects

Since the discovery of Prontosil in 1932, sulfonamide antibiotics have been used to combat a wide spectrum of bacterial infections, from acne to chlamydia and pneumonia. However, their side effects can include serious neurological ...

Medical research created May 23, 2013 | popularity 3 / 5 (1) | comments 0 | with audio podcast

Scientists discover molecule triggers sensation of itch

Scientists at the National Institutes of Health report they have discovered in mouse studies that a small molecule released in the spinal cord triggers a process that is later experienced in the brain as ...

Medical research created May 23, 2013 | popularity 5 / 5 (3) | comments 0 | with audio podcast

Discarded immune cells induce the relocation of stem cells

Spanish researchers have discovered that the daily clearance of neutrophils from the body stimulates the release of hematopoietic stem cells from the bone marrow into the bloodstream, according to a report published today ...

Medical research created May 23, 2013 | popularity 5 / 5 (2) | comments 0


Seniors more likely to crash when driving with pet, study finds

(HealthDay)—Animals make great companions for senior citizens, but elderly people who always drive with a pet in the car are far more likely to crash than those who never drive with a pet, researchers have ...

First drug to improve heart failure mortality in over a decade

Coenzyme Q10 decreases all cause mortality by half, according to the results of a multicentre randomised double blind trial presented today at Heart Failure 2013 congress. It is the first drug to improve heart failure mortality ...

Heart failure accelerates male 'menopause'

Heart failure accelerates the aging process and brings on early andropausal syndrome (AS), according to research presented today at the Heart Failure Congress 2013. AS, also referred to as male 'menopause', was four times ...

Death highest in heart failure patients admitted in January, on Friday, and overnight

Mortality and length of stay are highest in heart failure patients admitted in January, on Friday, and overnight, according to research presented today at the Heart Failure Congress 2013. The analysis of nearly 1 million ...

Feds fight morning-after pill age ruling in NY

(AP)—Department of Justice lawyers have again asked a federal appeals court in New York to delay lifting age restrictions and prescription requirements on an emergency contraceptive popularly known as the morning-after ...

New immune system discovered

(Medical Xpress)—A research team, led by Jeremy Barr, a biology post-doctoral fellow, unveils a new immune system that protects humans and animals from infection.