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Cell Metabolism

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There is hope for a future cure of insulin-dependent (type 1) diabetes from Jerusalem researchers who have identified the key signal that initiates production of insulin-producing beta cells in the pancreas.They call their discovery a breakthrough that could help researchers find ways to restore or increase beta cell function in people with this type of diabetes, which usually appears in childhood.The work on the multi-year project was led by Prof. Yuval Dor of the Hebrew University of Jerusalem’s Institute for Medical Research Israel-Canada and colleagues from the Hadassah University Medical Center, with assistance from the diabetes section of the Roche pharmaceuticals company. The study was published in a recent issue of the journal“Our work shows that as the glucose level is increased in the blood, it tells the beta cells to regenerate,” said Dor. “It’s not blood glucose per se that is the signal, but the glucose-sensing capacity of the beta cell that’s the key for regeneration.”This was the first time that this sensing of a high level of glucose has been shown to be the “trigger” that induces beta cells to regenerate.In persons suffering from type 1 (juvenile-onset) diabetes, the immune system launches a misguided attack on the insulin producing beta cells as if they were foreign cells, resulting in the cells’ decline of insulin production and eventual loss of function.Without insulin, the body’s cells cannot absorb glucose from the blood and use it for energy. As a result, glucose accumulates in the blood, leaving the body’s cells and tissues starved for energy. That’s why people with the disease must inject insulin and monitor their blood glucose levels carefully several times a day. To cure type 1 diabetes, methods must be developed to increase beta cell replication and mass, thus the potential therapeutic importance of the current study.In their work, Dor, along with co-lead author Prof. Benjamin Glaser of the Hadassah University Medical Center, used a genetic system to destroy 80 percent of the insulin-producing cells in the pancreases of adult mice, rendering the mice diabetic.When the researchers compared these mice with control mice, they found that those with diabetes and elevated blood glucose levels had regenerated a greater number of new beta cells than mice without diabetes, suggesting that glucose may be a key player in beta cell regeneration. They also found that a glucose-sensing enzyme in the cells, glucokinase, is the key molecule that triggers the beta cell regeneration.“This means that the more work that beta cells are required to do [that is, the more ‘stressed’ they are], the more of themselves they make,” said graduate student Shay Porat, who, along with fellow graduate student Noa Weinberg, spearheaded the study, which was funded with the support of the Juvenile Diabetes Research Foundation.Because this study showed that regeneration depends on glucokinase levels, the finding may pave the way for developing a new kind of drug to modulate glucokinase or other steps in the glucose-sensing pathway to direct beta cells down the path of regeneration and replication.If such a mechanism that prevents the immune system from attacking beta cells in the first place is discovered, the combined treatment could help pave the way toward a full cure for type 1 diabetes. Further research in this area is proceeding, with the eventual goal of progressing toward human clinical trials.Prof. Aaron Hanukoglu, a type 1 diabetes expert at Wolfson Medical Center in Holon and Tel Aviv University’s Sackler Medical School, commented: “The incidence of type 1 has been rising persistently for several decades in many countries around the the world including Israel, and many research groups are trying to find a cure or prevention for this chronic disease.This Jerusalem research on mice is very elegant and laborious, and if proven true in humans, it may lead to development of therapeutic measures for regeneration of pancreatic beta cells and a cure to juvenile-onset diabetes.”Research on animal models, Hanukoglu added, cannot always be successfully applied in humans, and the development of therapies based on animal studies may take many years.“But as a pediatric endocrinologist treating children and adolescents, I very much hope that the study results will open new avenues for therapy,” he said.