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 Plasmonic biosensors enable development of new easy-to-use health tests
14.12.2017 | Aalto University

nachricht ASU scientists develop new, rapid pipeline for antimicrobials
14.12.2017 | Arizona State University

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: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

Im Focus: Successful Mechanical Testing of Nanowires

With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong

Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Plasmonic biosensors enable development of new easy-to-use health tests

14.12.2017 | Health and Medicine

New type of smart windows use liquid to switch from clear to reflective

14.12.2017 | Physics and Astronomy

BigH1 -- The key histone for male fertility

14.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>