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Missing link detected in insulin mechanism

HANOVER, NH 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 in
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Contact: Andy Nordhoff
dms.communications@dartmouth.edu
603-650-1492
Dartmouth Medical School
19-Jun-2003


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