Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Joslin-led study reveals new findings on insulin signaling in the liver

15.05.2006


New findings may one day advance treatments to prevent type 2 diabetes and metabolic syndrome



Insulin uses two distinct mechanisms to control glucose and the metabolism of blood fats (lipids) in the liver, a new Joslin Diabetes Center-led study has discovered. Failures in each of these networks can lead to serious health problems: the breakdown of glucose metabolism that can lead to type 2 diabetes, and the malfunction of lipid metabolism contributing to metabolic syndrome, which is a cluster of conditions that puts people at increased risk of heart disease, vascular disease and type 2 diabetes.

The new study, led by C. Ronald Kahn, M.D., and Cullen Taniguchi, M.D., Ph.D., of Joslin Diabetes Center in Boston and their colleagues, is published in the May edition of Cell Metabolism. The findings open the door to the development of new treatments that one day may target directly the conditions that contribute to type 2 diabetes and the metabolic syndrome.


"Patients with the metabolic syndrome have high levels of both glucose and lipids in the blood. We now understand that insulin that controls the pathways that control glucose levels are different from those that regulate lipid levels. By targeting these specific pathways, we might be able to improve problems with glucose metabolism, lipid metabolism or both," says Dr. Kahn, President of Joslin Diabetes Center and Mary K. Iacocca Professor of Medicine at Harvard Medical School.

Diabetes affects an estimated 20.8 million children and adults in the United States -- 7 percent of the population. An estimated 14.6 million Americans have been diagnosed, leaving 6.2 million Americans unaware that they have the disease. In addition, 41 million Americans are thought to have pre-diabetes, or elevated blood glucose levels that put them at risk for developing type 2 diabetes. If untreated or poorly treated, diabetes can lead to blindness, kidney disease, stroke, nerve damage and circulation problems that can result in limb amputations.

Patients generally are diagnosed with metabolic syndrome if they have three or more of the following conditions: abdominal obesity; high cholesterol levels or triglycerides; low levels of good cholesterol; high blood pressure; and high blood glucose. The metabolic syndrome has become increasingly common in the United States, and according to a recent survey, is seen in 24 percent of all adult Americans above age 20 and in about 40 percent of those above age 60.

Exploring the role of the liver The liver is the body’s primary chemical factory, and among its key roles is keeping glucose levels in the blood constant between meals. The liver also produces and packages cholesterol and triglycerides to send throughout the body. Insulin’s activity in the liver controls both of these processes, but, until now, researchers have not understood how insulin does its job.

"In one of its roles, insulin tells the liver that you have just eaten, that it can stop producing glucose since the food you have just eaten will, for a while, supply an adequate amount," says Dr. Taniguchi, a postdoctoral fellow in Joslin’s Section on Cellular and Molecular Physiology and lead author of the paper. "Insulin also is the trigger that tells the liver how to handle lipids. We have been trying for many years to understand how insulin provides these signals, and now we have shown that insulin controls each process differently."

Insulin drives the liver’s metabolic functions by activating a molecule called phosphoinositide 3-kinase (PI3K), which then recruits other enzymes to carry out its orders. While researchers knew that the PI3K pathway was important to insulin’s action, until now they didn’t know how insulin uses PI3K to control either glucose or lipid metabolism.

Using mice bred to lack specific subunits of the PI3K pathway, the researchers discovered that mice that could not activate the protein kinase Akt had increased glucose production in the liver, impaired glucose tolerance, and increased levels of insulin in the blood, all contributors to type 2 diabetes. On the other hand, those mice with defects in the atypical forms of the enzyme protein kinase C (PKC) had decreased lipids in the blood and reduced levels of a protein called SREBP, which is critical for regulating fatty acid and cholesterol in the blood. (This particular form of the PKC enzyme is distinct from the form known as PKC-beta, which is activated by high blood glucose and is linked to many diabetic complications, including those of the eye and the blood vessels.)

"People used to think that Akt controlled both glucose and the lipids in the liver," says Dr. Taniguchi. "Now we know that Akt has nothing to do with the lipids. Akt controls the glucose part and the atypical PKC controls the lipids part." He explains that some patients with fatty liver disease don’t have any glucose problems, while others with type 2 diabetes don’t have problems with their lipids. "Now that we have uncovered the important molecules for each condition," says Dr. Taniguchi, "we can begin to look for ways to specifically target just the lipids or just the glucose."

Marjorie Dwyer | EurekAlert!
Further information:
http://www.joslin.org

More articles from Health and Medicine:

nachricht Hot cars can hit deadly temperatures in as little as one hour
24.05.2018 | Arizona State University

nachricht 3D images of cancer cells in the body: Medical physicists from Halle present new method
16.05.2018 | Martin-Luther-Universität Halle-Wittenberg

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: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

When corals eat plastics

24.05.2018 | Ecology, The Environment and Conservation

Surgery involving ultrasound energy found to treat high blood pressure

24.05.2018 | Medical Engineering

First chip-scale broadband optical system that can sense molecules in the mid-IR

24.05.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>