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Team reveals molecular mechanism underlying a form of diabetes
Date:9/8/2009

insulin secretion."

In a healthy individual, pancreatic beta cells respond to changes in blood glucose levels by secreting the appropriate amount of insulin. Beta cell dysfunction may result in abnormal blood glucose regulation and severe diabetes.

"A key finding in this study was identifying the ankyrin protein in the pancreatic beta cell, which is a type of excitable cell. Ankyrins also play critical roles for ion channel regulation in other excitable cells, such as neurons and heart cells called cardiomyocytes," said the paper's senior author, Peter Mohler, Ph.D., University of Iowa associate professor of internal medicine and a Pew Scholar.

Specifically, the team found that the gene mutation prevents most KATP channels from binding with ankyrin, which typically acts as a cellular chaperone. This failure prevents the KATP channels from reaching their normal destination in the cell membrane.

"Ankyrin proteins are like cellular taxi-cabs that carry passenger channels to the cell membrane. In the case of this KATP gene mutation, the ankyrin and channels cannot interact properly, and so the channels basically 'miss their ride' and do not get to the desired location," Mohler said.

The team also found that the few mutant KATP channels that do reach the pancreatic cell membrane do not respond to alterations in cellular metabolism. As a result, the pancreatic beta cells do not release insulin appropriately.

"This is another exciting example of how understanding the basis of rare disease has provided unexpected and fascinating insight into the molecular pathways that govern human physiology," Mohler said.


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Contact: Becky Soglin
becky-soglin@uiowa.edu
319-356-7127
University of Iowa
Source:Eurekalert

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