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 Oestrogen regulates pathological changes of bones via bone lining cells
28.07.2017 | Veterinärmedizinische Universität Wien

nachricht Programming cells with computer-like logic
27.07.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Abrupt motion sharpens x-ray pulses

Spectrally narrow x-ray pulses may be “sharpened” by purely mechanical means. This sounds surprisingly, but a team of theoretical and experimental physicists developed and realized such a method. It is based on fast motions, precisely synchronized with the pulses, of a target interacting with the x-ray light. Thereby, photons are redistributed within the x-ray pulse to the desired spectral region.

A team of theoretical physicists from the MPI for Nuclear Physics (MPIK) in Heidelberg has developed a novel method to intensify the spectrally broad x-ray...

Im Focus: Physicists Design Ultrafocused Pulses

Physicists working with researcher Oriol Romero-Isart devised a new simple scheme to theoretically generate arbitrarily short and focused electromagnetic fields. This new tool could be used for precise sensing and in microscopy.

Microwaves, heat radiation, light and X-radiation are examples for electromagnetic waves. Many applications require to focus the electromagnetic fields to...

Im Focus: Carbon Nanotubes Turn Electrical Current into Light-emitting Quasi-particles

Strong light-matter coupling in these semiconducting tubes may hold the key to electrically pumped lasers

Light-matter quasi-particles can be generated electrically in semiconducting carbon nanotubes. Material scientists and physicists from Heidelberg University...

Im Focus: Flexible proximity sensor creates smart surfaces

Fraunhofer IPA has developed a proximity sensor made from silicone and carbon nanotubes (CNT) which detects objects and determines their position. The materials and printing process used mean that the sensor is extremely flexible, economical and can be used for large surfaces. Industry and research partners can use and further develop this innovation straight away.

At first glance, the proximity sensor appears to be nothing special: a thin, elastic layer of silicone onto which black square surfaces are printed, but these...

Im Focus: 3-D scanning with water

3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects

A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

 
Latest News

New 3-D imaging reveals how human cell nucleus organizes DNA and chromatin of its genome

28.07.2017 | Health and Medicine

Heavy metals in water meet their match

28.07.2017 | Power and Electrical Engineering

Oestrogen regulates pathological changes of bones via bone lining cells

28.07.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>