UCI researchers receive $2.27M to develop innovative methods of treating Type 1 diabetes.

Two UC Irvine research groups have received $2.27 million from the JDRF to develop innovative methods of treating and possibly curing Type 1 diabetes.

The JDRF, formerly the Juvenile Diabetes Research Foundation, awarded one grant to Jonathan Lakey, associate professor of surgery and biomedical engineering, and Elliot Botvinick, assistant professor of surgery and biomedical engineering; and another to Weian Zhao, assistant professor of pharmaceutical sciences and biomedical engineering. Lakey and Zhao are affiliated with the campus's Sue & Bill Gross Stem Cell Research Center.

With $1.27 million in funding over three years, Lakey and Botvinick will try to find a way to successfully transplant encapsulated, stem cell-created pancreatic islets. In Type 1 diabetes, the pancreas cannot produce insulin - a hormone key to regulating carbohydrate and fat metabolism in the body - making daily insulin treatments necessary.

The pancreas, an organ about the size of a hand, is located behind the lower part of the stomach. It makes insulin and enzymes that help the body digest and use food. Throughout the pancreas are clusters of cells called the islets of Langerhans. Islets are composed of several types of cells, including beta cells that make insulin.

In a previous study, Lakey helped show that transplanted encapsulated islets can create and secrete insulin. A major hurdle, though, is overcoming immune-system rejection of these transplanted islets.

The Lakey-Botvinick team - which includes researchers and products from UC Irvine, the University of Oxford, the Netherlands' University of Groningen, Eastern Virginia Medical School, Islet Sheet Medical in San Francisco, Islet Sciences in New York and Danish pharmaceutical company Novo Nordisk - will explore the use of isolated islets in which the cells are encased in an ultrapure algae membrane.

The encapsulation chemistry allows for selective permeability, meaning that some small molecules, such as glucose and insulin, can pass across the barrier, while large antibodies and immunological molecules are blocked from entering into the space containing the islets.

"Perhaps the greatest challenge in the field of islet transplantation is to make the metabolic benefits available to patients with Type 1 diabetes without the need for chronic immunosuppression," said Lakey, who's also director of UC Irvine Health's Clinical Islet Program. "I believe that this technology has great promise for realizing our goal. And this welcome support from the JDRF should speed our progress."

With the other grant, Zhao and his colleagues will try to develop an insulin sensor for the JDRF's Artificial Pancreas Project, which supports the creation of an automated system to dispense insulin based on real-time changes in blood sugar levels. Central to such a device is a mechanism that can accurately determine blood insulin amounts to provide feedback control for the artificial pancreas.

Existing systems deliver insulin via a pump under closed-loop control using data from a continuous glucose sensor. They are, however, associated with severe risks - especially insulin overdose - when any of their components malfunction.

Zhao will receive $1 million for the two-year effort, with the potential for further funding if his team comes up with a promising model. "Integrating a real-time insulin sensor into the artificial pancreas system will allow us to precisely monitor and control the levels of both sugar and insulin, ultimately leading to safe and effective management of diabetes," he said.

Other UC Irvine researchers involved in these projects include Bernard Choi, associate professor of surgery and biomedical engineering; Dr. Clarence Foster, clinical professor of surgery and chief of the School of Medicine's transplantation division; and Frank Zaldivar and Dr. Pietro Galassetti with the Institute for Clinical & Translational Science.

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