In a development that could potentially lead to new treatments for diabetes, researchers have found that a protein that regulates the development of nerve cells also plays a role in prompting cells in the pancreas to release insulin, a hormone that helps to maintain a normal level of blood sugar.
The researchers, who included one of Indian-origin, studied a group of proteins called neurotrophins, and in particular nerve growth factor (NGF).These proteins nurture the growth of neurons, the cells of the nervous system.
It has been known for some time that neurons and the pancreatic beta cells that reside in clusters called islets of Langerhans and produce insulin, have many similarities in molecular makeup and signalling receptors. This project was sparked by seeing NGF receptors present in beta-cells,” said one of the researchers Rejji Kuruvilla from Johns Hopkins University in Baltimore, Maryland, US.
Receptors are proteins on cell surfaces that respond to particular chemicals and have critical roles in biochemical mechanisms.
Both neurons and pancreatic beta cells have the receptors for neurotrophins.
The question was, Kuruvilla said: “What are these receptors doing outside the nervous system?”
It turns out that NGF performs a function in the mature pancreas that has nothing to do with supporting neurons.
Specifically, the research team traced a chain of biochemical signals showing that elevated blood glucose causes NGF to be released from blood vessels in the pancreas, and that the NGF signal then prompts pancreatic beta cells to relax their rigid cytoskeletal structure, releasing insulin granules into the blood stream.
Although beta cells also make NGF, the study published in the journal Developmental Cell, found that it was the NGF released from the blood vessels that is needed for insulin secretion.
Using genetic manipulation in mice and drugs to block NGF signalling in beta cells, they were able to disrupt distinct elements of this signalling sequence, to show that this classical neuronal pathway is necessary to enhance insulin secretion and glucose tolerance in mice.
Importantly, Kuruvilla and colleagues also found that NGF’s ability to enhance insulin secretion in response to high glucose also occurs in human beta cells.