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Stress peptide and receptor may have role in diabetes
Date:1/22/2010

the nature of the response or which cells or receptors were involved.

Prompted by evidence suggesting that CRF has an effect on beta cells, a team led by first author Mark O. Huising, Ph.D., and senior author Wylie Vale, a professor and head of the Salk Institute's Clayton Foundation Laboratories for Peptide Biology and holder of the Helen McLoraine Chair in Molecular Neurobiology, sought to verify that effect and determine its underlying mechanism. Working with cell lines, pancreatic islets from mice and human donors, as well as mouse models, Vale's lab, which discovered CRF in the early 1980s, conducted a series of experiments that collectively demonstrated the presence and actions of CRFR1 in the islets.

"We found that beta cells in the pancreas actually express the CRFR1 receptor," explains Huising, a postdoctoral fellow in the Clayton Foundation Laboratories. "And once we had established the presence of CRFR1 in the islet, we started filling in the blanks, trying to learn as much about pancreatic CRFR1 as we could."

What they discovered was that beta cells exposed to CRF, one of the peptides that activate the CRFR1 receptor, can respond in at least two ways. First, they increase their secretion of insulin if they simultaneously encounter high levels of glucose. The higher the levels of glucose, the more insulin they release in response to CRF and the more rapidly blood levels of glucose are reduced.

Working in collaboration with a group at the Panum Institute in Copenhagen, the researchers went on to establish that beta cells exposed to CRF also activate the MAPK pathway, which is a key pathway implicated in beta cell division. Mature, differentiated beta cells can divide, albeit slowly, but if they are exposed to a molecule that will activate the CRFR1 receptor, they will start to divide somewhat more rapidly, which is especially relevant in the context of type 1 diabetes.

"The thinking is that type 1 diabetic patie
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Contact: Gina Kirchweger
kirchweger@salk.edu
885-845-341-001-340
Salk Institute
Source:Eurekalert

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