07:09am Tuesday 07 July 2020

The little enzyme that could: Glucokinase’s role in triggering beta cell regeneration may clear the path for better therapies

JDRF-funded researchers in Israel found for the first time that a high rate of glucose metabolism – the process in which glucose is converted into energy – prompts existing insulin-producing beta cells to form new beta cells in mice. Published in the April 6 issue of Cell Metabolism, the breakthrough findings give us a new understanding of what actually elicits beta cell regeneration. Regeneration lies not in blood glucose itself, suggests the study, but in the glucose-sensing capability of the beta cell.

Over the course of five years, Yuval Dor, Ph.D. (a professor at the Institute for Medical Research Israel-Canada, the Hebrew University of Jerusalem) and Benjamin Glaser, M.D. (of Hadassah Medical Center) conducted a series of experiments in which they used a genetic system to cause diabetes in adult mice by destroying 80 percent of their insulin-producing cells. When compared to control mice, the mice with diabetes whose blood glucose levels were elevated had regenerated more new beta cells than the mice without diabetes, suggesting the important role of glucose in beta cell regeneration.

With this in mind, the researchers then set out to understand how glucose played this role. By manipulating certain steps in the glucose metabolism pathway, they discovered that an enzyme called glucokinase – which sparks the first step in converting glucose to energy – also stimulates the replication of beta cells.

So, what does this mean for people with type 1 diabetes? Since glucokinase, rather than glucose itself, was found to be a key factor, the study implies that drugs which activate this enzyme may be more useful in prompting beta cells to regenerate than therapies that raise glucose levels. Elevated glucose levels can lead to complications such as organ damage and can even destroy more beta cells, so the possibility of using therapies that avoid this is excellent news.

Because of its ability to increase insulin production, this class of drugs that activates glucokinase is already being developed to treat type 2 diabetes. With new insight into the enzyme’s abilities, JDRF is hopeful that these drugs may also help restore beta cell function in people with both type 1 diabetes and type 2 diabetes.

JDRF has been at the helm of a novel and fast-growing field of research focused on finding ways to protect and regenerate insulin-producing cells in people who have diabetes or those who are at risk. We are excited by the innovative studies we fund like Dr. Dor’s, as new findings like this propel us forward on the path toward better treatments and a cure for type 1 diabetes.

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