Throughout National Diabetes Month, we will be sharing developments into Joslin’s unique approach for a permanent cure for type 1 diabetes. Our mission is to prevent, treat and cure diabetes so that one day there will be a world free of diabetes and its complications.
Peng Yi, Ph.D., has joined the research staff of Joslin Diabetes Center, bringing with him an impressive background in research on the replication and regeneration of pancreatic beta cells that applies to the treatment of both type 1 and type 2 diabetes. He joins a talented team of researchers focused on treating and ultimately curing type 1 diabetes as an Assistant Investigator in the Islet Cell and Regenerative Biology Section.
People with type 1 diabetes are unable to produce insulin because their immune system destroys their pancreatic beta cells, causing them to become dependent on insulin injections. Replenishing these insulin-producing cells is the goal of many type 1 researchers and Dr. Yi may have found just the way to do this.
While working at Harvard Stem Cell Institute (HSCI), Dr. Yi along with Doug Melton, Ph.D., co-director of the HSCI, Xander University Professor at Harvard University and co-chair of the Department of Stem Cell and Regenerative Biology, discovered the hormone betatrophin, which increases the production of new insulin-producing beta cells in the pancreas.
Dr. Yi and his team established an inducible insulin resistance mouse model, meaning that they were able to turn on and off the insulin resistance at will.
“Using this model, we discovered a new hormone called betatrophin that is released from the liver and fat, and we showed that the over-expression of betatrophin in the liver causes dramatic and specific pancreatic beta cell replication and beta cell mass expansion,” said Dr. Yi.
Dr. Yi believes that by utilizing Joslin’s resources and collaborating with notable members of the Joslin faculty, he will be able to further advance his research with betatrophin. His primary goal is to develop a betatrophin drug, which if successful will serve as a treatment and part of a cure for both type 1 and type 2 diabetes. To assemble this drug, Dr. Yi is continuing to collaborate with Dr. Melton’s lab at Harvard, Evotec, a German biotech firm, and Janssen Pharmaceuticals, a Johnson & Johnson company, which is the only company that the compound has been licensed to.
“There are two sides of the treatment or cure – you have to shut down the autoimmune response to the beta cells and expand the beta cell mass,” explained Dr. Yi. “I think betatrophin may be a promising way to expand the beta cells mass for people [with type 1 diabetes] and slow down the progression of diabetes before, or at the time of diagnosis.”
He continued, “type 2 diabetes is very similar – at the late stage of type 2 people have less beta insulin, so they have to inject insulin. But if you can find a way to sensitize tissues to insulin signaling, you still need to repopulate your beta cells mass.”
Dr. Yi hopes a betatrophin drug will capitalize on the “honeymoon stage” of type 1 diabetes, which can happen after a patient is diagnosed. For reasons unknown, some patients experience a leveling of blood glucose numbers coupled with reduced insulin requirements. But this stage does not last.
“If you can diagnosis the patients in the early stages of diabetes, when their beta cells are not destroyed completely, then you maybe can use the betatrophin to prolong or postpone the development of type 1 diabetes, and the same case is with type 2 diabetes,” explained Dr. Yi.
Aside from focusing on the development of a betatrophin drug, Dr. Yi’s new lab is also concentrating on the mechanisms of how betatrophin works. His team wants to know how and why betatrophin shows up in the body, and if it binds to other proteins to do its job or if it works alone.
Specifically, Dr. Yi and his lab are focusing on why and how betatrophin stimulates beta cell proliferation, and they are particularly interested in identifying the responsible receptor, which is integral for large screen drug screenings for a betatrophin drug.
Dr. Yi’s lab hopes to recruit Joslin patients for a clinical trial, which would help Dr. Yi and his team better understand how betatrophin behaves in humans as compared to how it behaves in mice. They are also examining betatrophin’s potential as a diagnosis marker to evaluate the particular risk an individual has for developing type 2 diabetes. This will be particularly helpful for people who develop diabetes when they are only slightly overweight due to their genetic predisposition.
With all of these projects underway, Dr. Yi is excited about his research and the opportunity to work within the Joslin community.
“Joslin is the best place to study diabetes [because] we are surrounded with all these well-known diabetes researchers,” said Dr. Yi. “But this is just the beginning, we have huge hopes for [betatrophin research], we are not done yet.”
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