Findings may provide new insights into diabetes; suggest novel targets for drug intervention

January 27, 2016

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 patients usually have a few beta cells left in their pancreas, so those remaining beta cells, though not enough to control glucose levels, may seed a population of regenerating beta cells," Huising says.

While a few gut peptides termed incretins, which are currently used to increase insulin secretion in patients, have also been shown to accelerate beta cell division, the Vale group's findings suggest an incretin-like effect for a peptide normally associated with the stress response.

"Anything we can find out that will drive proliferation or the division of beta cells is very interesting, and 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."

These results emphasize the complexity of metabolic disorders and identify novel targets to treat diabetes and obesity. One of the key questions remaining for Vale and his group is under what conditions the pancreatic CRFR1 system is utilized and gets activated.

"We know what it can do, but we don't fully understand the physiological circumstances under which it does it," Vale says. "This receptor appears to be important within the pancreas. What we haven't determined, though, is whether this is a stress-linked phenomenon because we still have questions regarding the source of the hormone that acts on pancreatic CRFR1. We would like to know where it is coming from to determine if it is released in stressful conditions to bring about the effects we observed." .

Source: Salk Institute for Biological Studies