Salk scientists have discovered that the neuropeptide corticotropin-releasing factor (CRF), which initiates the stress response in the brain, also plays a role in the pancreas, where it increases insulin secretion and promotes the division of the insulin-producing beta cells. The findings may provide new insights into diabetes, particularly type 1, as well as suggest novel targets for drug intervention.
CRF, in concert with its receptor, CRFR1, has long been known as key to the body's response to various forms of stress, but the pair is also involved in many more processes. As early as the 1980s, studies had suggested that pancreas cells can respond to CRF, but the few limited observations did not demonstrate the nature of the response.
Working with cell lines, pancreatic islets from mice and human donors, as well as mouse models, Wylie 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.
What the team 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.
"Being able to stimulate beta cells to divide a little faster may be part of a solution that may ultimately, hopefully, allow management of type 1 diabetes," Vale says. "But because it is an autoimmune condition, making the cells divide won't be enough. That is why researchers are working hard to solve the problem of destruction of beta cells."