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 New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>