Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Missing link detected in insulin mechanism

20.06.2003


Protein could provide clues for understanding type two diabetes



Along the multifaceted insulin pathway, Dartmouth Medical School biochemists have found a missing link that may spark the connection for glucose to move into cells. The discovery is another strand in the remarkable web of molecular signals that regulate traffic through cells and helps elucidate crucial aspects of how the hormone insulin regulates a membrane movement process.

The work is being discussed June 21 at the Endocrine Society meeting in Philadelphia by Dr. Gustav Lienhard, professor of biochemistry, who also reported the results in a recent issue of the Journal of Biological Chemistry with colleagues from Dartmouth and Harvard.


Insulin acts to maintain the appropriate level of glucose in the blood. After eating, blood glucose rises, triggering release of insulin from the pancreas to lower the sugar level. One way insulin does that is to accelerate the removal of glucose from blood and into muscle and fat cells. Key aspects of the mechanism for insulin to stimulate this glucose uptake remain to be sorted out.

A conundrum is that muscle and fat cells have proteins known as transporters for ferrying glucose, but these transporters are in the wrong place. Instead of being in the cell’s surface membrane where glucose can climb aboard for passage, they are in vesicles within the cell. So insulin, pressing on a muscle or fat cell, prods these vesicles inside the cell to fuse with the surface membrane, putting the transporters where they can ferry the glucose into the cell. Suddenly the surface membrane has many transporters and glucose can enter the cell rapidly.

Lienhard likens the process to a room with too few doors. "You have a lot of people wanting to get into the room that only has two doors so they would all have to go through these two doors. But inside the room is a stack of doors. People are the glucose molecules and the doors are the transporters; in response to insulin, these doors get shoved into the walls of the room and more people can get into the room quickly."

Lienhard leads a team studying how insulin impinging on the outside of the cell spurs these transporter-containing vesicles to move toward and fuse with the cell surface. It involves linking up two specialized areas of cell biology: cell signaling and membrane trafficking.

Insulin binding to its receptor on the outside of the cell membrane initiates a series of actions. That receptor extends through to the inner surface of the membrane and triggers signaling steps, or a signal transduction pathway, that eventually leads to the vesicle movement and fusion.

The Dartmouth researchers have found a protein that seems to bridge the signaling and membrane movement, a span between the signal transduction pathway and the machinery that controls the fusion of the transporter-containing vesicles with the cell surface.

"That was a missing link in this field. If we’re right, this looks like a key protein that connects signaling to trafficking. At the end of the signal transduction pathway, we found a protein that’s modified by phosphorylation--by putting phosphate groups on it--and this protein also acts on a key protein component in the machinery for vesicle movement and fusion," Lienhard says.

This protein could provide clues for understanding type two diabetes. A hallmark of the illness is insulin resistance: muscle and fat tissues do not respond adequately to insulin. The transporters they need on their cell surface are trapped inside and it takes a higher concentration of insulin to move additional transporters to the cell surface. Lienhard stresses that studies of the protein in diabetic rodent models need to be done.

The findings could also shed light on how hormones regulate movement of membrane proteins in general, Lienhard adds. "The protein has a widespread tissue distribution. It is found in all the major tissues in the body--brain, liver, kidney, so it could function in other systems where a hormone treatment causes the rapid movement of proteins to the cell surface."

The researchers used a cultured fat cell line that originated from mice. Once they found the protein, they were able to identify it by comparing its amino acid sequence to the gene database.

Contact:

Andy Nordhoff
e-mail: dms.communications@dartmouth.edu

Andy Nordhoff | EurekAlert!
Further information:
http://www.dartmouth.edu

More articles from Life Sciences:

nachricht Colorectal cancer: Increased life expectancy thanks to individualised therapies
20.02.2020 | Christian-Albrechts-Universität zu Kiel

nachricht Sweet beaks: What Galapagos finches and marine bacteria have in common
20.02.2020 | Max-Planck-Institut für Marine Mikrobiologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A step towards controlling spin-dependent petahertz electronics by material defects

The operational speed of semiconductors in various electronic and optoelectronic devices is limited to several gigahertz (a billion oscillations per second). This constrains the upper limit of the operational speed of computing. Now researchers from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg, Germany, and the Indian Institute of Technology in Bombay have explained how these processes can be sped up through the use of light waves and defected solid materials.

Light waves perform several hundred trillion oscillations per second. Hence, it is natural to envision employing light oscillations to drive the electronic...

Im Focus: Freiburg researcher investigate the origins of surface texture

Most natural and artificial surfaces are rough: metals and even glasses that appear smooth to the naked eye can look like jagged mountain ranges under the microscope. There is currently no uniform theory about the origin of this roughness despite it being observed on all scales, from the atomic to the tectonic. Scientists suspect that the rough surface is formed by irreversible plastic deformation that occurs in many processes of mechanical machining of components such as milling.

Prof. Dr. Lars Pastewka from the Simulation group at the Department of Microsystems Engineering at the University of Freiburg and his team have simulated such...

Im Focus: Skyrmions like it hot: Spin structures are controllable even at high temperatures

Investigation of the temperature dependence of the skyrmion Hall effect reveals further insights into possible new data storage devices

The joint research project of Johannes Gutenberg University Mainz (JGU) and the Massachusetts Institute of Technology (MIT) that had previously demonstrated...

Im Focus: Making the internet more energy efficient through systemic optimization

Researchers at Chalmers University of Technology, Sweden, recently completed a 5-year research project looking at how to make fibre optic communications systems more energy efficient. Among their proposals are smart, error-correcting data chip circuits, which they refined to be 10 times less energy consumptive. The project has yielded several scientific articles, in publications including Nature Communications.

Streaming films and music, scrolling through social media, and using cloud-based storage services are everyday activities now.

Im Focus: New synthesis methods enhance 3D chemical space for drug discovery

After helping develop a new approach for organic synthesis -- carbon-hydrogen functionalization -- scientists at Emory University are now showing how this approach may apply to drug discovery. Nature Catalysis published their most recent work -- a streamlined process for making a three-dimensional scaffold of keen interest to the pharmaceutical industry.

"Our tools open up whole new chemical space for potential drug targets," says Huw Davies, Emory professor of organic chemistry and senior author of the paper.

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

70th Lindau Nobel Laureate Meeting: Around 70 Laureates set to meet with young scientists from approx. 100 countries

12.02.2020 | Event News

11th Advanced Battery Power Conference, March 24-25, 2020 in Münster/Germany

16.01.2020 | Event News

Laser Colloquium Hydrogen LKH2: fast and reliable fuel cell manufacturing

15.01.2020 | Event News

 
Latest News

Journey to the center of Mars

20.02.2020 | Physics and Astronomy

Laser writing enables practical flat optics and data storage in glass

20.02.2020 | Physics and Astronomy

New graphene-based metasurface capable of independent amplitude and phase control of light

20.02.2020 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>