Navigation Links
Novel link between excessive nutrient levels and insulin resistance
Date:2/21/2008

La Jolla, CA For quite some time now, scientists suspected the so-called hexosamine pathway a small side business of the main sugar processing enterprise inside a cell to be involved in the development of insulin resistance. But they could never quite put their finger on the underlying mechanism.

Now, researchers at the Salk Institute for Biological Studies have uncovered the long-missing molecular link: the enzyme OGT (short for O-linked -N-acetylglucosamine transferase), the last in a line of enzymes that shuttle sugars through the hexosamine pathway.

Their study revealed that OGT slams the brake on insulin signaling soon after insulin fires up the machinery that pulls glucose from the blood stream and squirrels it away inside liver or stashes the surplus energy in fat pads.

For the first time we have a real understanding of how the insulin signaling system is turned on and off, says Howard Hughes Medical Investigator Ronald M. Evans, Ph.D., a professor in the Salk Institutes Gene Expression Laboratory, who led the study that appears in the Feb. 21 issue of Nature.

He hopes that this could lead to a new class of insulin-sensitizing drugs that loosen the brake and let insulin work a little bit longer.

When insulin binds its receptor on the cell surface it sets off a cascade of intracellular signals resulting in the production of PIP3, a specialized lipid molecule that masterminds a whole army of molecules that work together to synthesize and store carbohydrates, lipids and proteins. But turning on a physiological process is only half the story, explains Evans. You also need instructions that tell the cell to get off the accelerator and put on the brake.

Postdoctoral researcher and first author Xiaoyong Yang, Ph.D., discovered that PIP3 oversees both. His experiments revealed that within minutes activation of the insulin signaling network coaxes OGT out of the nucleus and into the cytoplasm. It travels to the plasma membrane and hooks up with PIP3.

It uses a novel PIP3 binding domain to interact with the same lipid that just turned on the system, describes Xiaoyong. After OGT is recruited to the plasma membrane it starts turning off the system.

It accomplishes this task by tagging key members of the insulin signaling network with sugar molecules, specifically O-linked -N-acetylglucosamine or O-GlcNAc, which are produced by the hexosamine pathway.

Since the amount of O-GlcNAc is directly tied to availability of glucose, lipids and other nutrients in the bloodstream, the researchers believe that the hexosamine pathway acts as fuel gauge, protecting the bodys cells against the toxic effects of too much glucose and other high-energy molecules.

Excessive quantities of nutrients the result of a lifestyle where food is plentiful and exercise is optional drive O-GlcNAc levels up, which in turn dampen the insulin response, paving the way for a relentless progression of insulin resistance.

Though it may not be as simple as that, when Xiaoyong put OGT into overdrive in the livers of mice, the animals developed insulin resistance and abnormal blood lipid levels, emphasizing the importance of the hexosamine pathway for the development of insulin resistance, the first step towards full-blown type 2 diabetes.

Most people with insulin resistance go on to develop type 2 diabetes within 10 years, unless they lose 5 to 7 percent of their body weightapproximately 10 to 15 pounds for someone who weighs 200 poundsby making modest changes in their diet and level of physical activity. But making permanent lifestyle changes is difficult and studies predict that one in three Americans born in the year 2000 will develop diabetes in their life time. A similar fate awaits most developed nations.


'/>"/>

Contact: Gina Kirchweger
kirchweger@salk.edu
858-453-410-01340
Salk Institute
Source:Eurekalert

Related medicine news :

1. Novel organic metal hybrids that will revolutionize materials science and chemical engineering
2. Novel mathematical model predicts new wave of drug-resistant HIV infections in San Francisco
3. Novel approach strips staph of virulence
4. UCSD research team identifies novel anticancer drug from the sea
5. Novel compound may lessen heart attack damage
6. Novel molecules developed at UB can boost vaccine potency
7. Novel small molecule therapy shows benefit for anemic patients via hydration of red blood cells
8. Novel vaccine concept developed by scientists at the Wistar Institute
9. Tibotec Pharmaceuticals a Respectful Partner to HIV Community in Pricing of Novel New HIV NNRTI, INTELENCE
10. Millennium and Harvard Medical School Sign Cooperative Agreement for Research in Novel Field of Cancer Biology
11. Statement by AARP CEO Bill Novelli on President Bushs State of the Union
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:12/5/2016)... Lakes, NJ (PRWEB) , ... December 05, 2016 ... ... recording studio teaming up on new songs with prolific Songwriter-Producer Corey “Chorus” Gibson ... Foxx, Kelly Rowland, Ciara, Brandy…just to name a few.     https://twitter.com/coreychorus , ...
(Date:12/5/2016)... ... December 05, 2016 , ... ... moisture measurements are consistently correct. However, regular performance testing is often neglected ... offers a solution: SmartCal™ . This innovative test substance offers a ...
(Date:12/4/2016)... York, NY (PRWEB) , ... December 03, 2016 ... ... largest non-profit organization devoted exclusively to funding innovative lymphoma research and serving the ... services – hosted its first Swirl: A Wine Tasting Event in New York ...
(Date:12/4/2016)... ... 04, 2016 , ... "Pro3rd Displace is a set of ... displacement design elements," said Christina Austin - CEO of Pixel Film Studios. ... of design styles that include both left aligned and right aligned options for ...
(Date:12/2/2016)... , ... December 02, 2016 , ... Lori G. ... Traurig, LLP’s Atlanta office, will speak at the American Conference Institute’s 21st Drug ... Traurig is also a Lead Sponsor of the conference. , Cohen, who chairs the ...
Breaking Medicine News(10 mins):
(Date:12/5/2016)... -- M ichael Moore ... Chairman   Mission Therapeutics, a drug discovery and ... treat cancer, neurodegenerative and other diseases, announces that Dr ... January 1 st 2017. Dr Colin Goddard ... in July 2015. Michael Moore , Mission,s Founder Chairman, ...
(Date:12/4/2016)... 3, 2016 Johnson & Weaver, LLP announces that ... of Zimmer Biomet Holdings, Inc. (NYSE: ZBH ) ... 31, 2016 (the "Class Period"). Zimmer Biomet provides ... orthopaedic reconstructive products, such as knee and hip reconstructive products. ... , , ...
(Date:12/4/2016)... , Dec. 3, 2016  Results from the ... SelG1), an anti-P-selectin antibody, reduced the median annual rate ... to placebo (1.63 vs 2.98, p=0.010) in patients with ... that the data are being featured in the official ... of Hematology (ASH) Annual Meeting and presented during the ...
Breaking Medicine Technology: