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Joslin Hosts Symposium on Type 1 Diabetes Research

Monday, May 20, 2013

On Monday, May 6, Joslin Diabetes Center brought together some of the best minds in type 1 diabetes research for a day-long symposium covering the field’s cutting-edge research.

George King, M.D., Chief Scientific Officer at Joslin Diabetes Center and Professor of Medicine at Harvard Medical School

The morning began with a welcome from John Brooks, President and CEO of Joslin. “Type 1 is a major part of our focus,” he said. “We want to continue to devote resources and find a real solution.” George King, Chief Scientific Officer, and Jeffrey Flier, Dean of Harvard Medical School, both discussed Joslin’s long history of involvement in type 1 diabetes research, from the administering of one of the first insulin treatments in the 1920s to the realization in the early 1980s that type 1 diabetes was not in fact a sudden onset disease, but one that built gradually in the immune system over time.

Type 1 diabetes is diagnosed when the immune system attacks and destroys beta cells, meaning that the body’s essential hormone insulin can no longer be produced. Two speakers of the day’s eight discussed the first part of this problem--addressing the autoimmunity responsible for beta cell attack.

Matthias von Herrath, M.D., professor at the La Jolla Institute for Allergy and Immunology, spoke about uncovering the triggers of autoimmunity. In his talk, he emphasized the point that whatever causes the destruction of beta cells typically occurs gradually over months and years and doesn’t act randomly. Studies in human type 1 diabetes, indicate the beta cells get wiped out completely in some lobes of the pancreas before beta cells in other lobes are attacked.

“It indicates...that there might be something that annoys the lobes in a repeated fashion and these lobes become sensitive,” he said. He suggested something analogous to a herpes virus, which is known to act in this fashion, could be involved though there is no firm evidence yet of such a virus contributing to beta cell destruction in human type 1 diabetes.

Later in the day, Emil Unanue, M.D., the Paul and Ellen Lacy Professor in the Division of Immunobiology at Washington University School of Medicine, discussed his work on what happens to T cells that makes them attack the insulin-secreting cells--the very root of autoimmunity. His research suggests that in people with type 1 diabetes, something goes wrong as T cells are trained to discriminate between healthy cells and infected cells or infectious agents that need to be eliminated.

Developing T cells are exposed to molecules resembling common proteins in the body, such as pieces of the insulin. As a result of this “training,” mature T cells recognize those proteins as part of the normal biology. In people with type 1 diabetes, however, the training goes wrong and insulin is mistaken for a foreign antigen, such as a virus, that needs to be eradicated. Dr. Unanue’s research is beginning to unravel where the missteps in T cell training actually occur.

Susan Bonner-Weir, Ph.D., Senior Investigator in the Section on Islet Cell & Regenerative Biology at Joslin Diabetes Center and Professor of Medicine at Harvard Medical School

The other part of type 1 diabetes--the lack of insulin secretion in response to glucose--was also addressed throughout the day. Joslin’s Susan Bonner-Weir, Ph.D., professor at Harvard Medical School, talked about her search for ways to replace beta cells using the duct cells of the pancreas.

Duct cells form the tubes of the pancreas that carry digestive juices into the intestine. Dr. Bonner-Weir discussed a number of studies showing that duct cells can replicate and eventually produce insulin-producing cells under the right conditions. When a pancreas is under stress--whether during pregnancy or after a gastric bypass surgery--researchers have seen the replication of insulin-secreting cells in the pancreas, but “it’s not the islet cells that are replicating, it’s the duct cells.” Her lab at Joslin is following up on this line of research.

Andrew Fyfe Stewart, M.D., Director of the Diabetes, Obesity and Metabolism Institute and the Irene and Dr. Arthur M. Fishberg Professor at Mount Sinai Medical School, talked about why human beta cells themselves hardly replicate at all. If beta cells replicated on their own, it would be easier to replenish the damaged stores of people with diabetes.

To find out if beta cells could be induced to replicate, Dr. Stewart took human islets and identified the parts of the machinery required for replication. In his talk, he likened this to having a list of parts a car needs to run without knowing how they all fit together.

A series of experiments described in his talk conducted by a member of his lab showed the location of each molecule on the list within the beta-cell--were the molecules inside the nucleus, where they could be used for replication, or were they in the cytoplasm, just floating around?

It turns out that many of the molecules that could be useful in replication float around in the cytoplasm, rather than in their workplace in the nucleus. It’s as though the carburetor and other engine parts were sitting in the backseat of your car, he said. Next step is to coax the important molecules into their necessary locations to see if beta cell replication could be activated.

Doug Melton, Ph.D., Xander University Professor, Harvard University, Co-Director & Co-Chair, Harvard Stem Cell Institute

The last talk of the day also dealt with beta cells, and how to create them. Doug Melton, Ph.D., the Xander University Professor at Harvard University, talked about two different ways to make beta cells.

First he talked about stem cells. Stem cells (be they embryonic cells or adult cells that have been induced back to an embryonic-like state) have an amazing ability to become any other living cell as long as the right genetic and external signals are applied. Dr. Melton’s lab has been working on getting “a molecular biography,” he said, of all the genetic steps required to make a stem cell a beta cell. In his talk, he hinted at a chemical breakthrough that could make the process more feasible.

Secondly, he talked about betatrophin, a recently discovered hormone capable of markedly stimulating the growth of beta cells. When expressed in the liver, “in a week we can double the amount of beta cells in a mouse,” he said. He cautioned that he’s not expecting betatrophin to be a cure-all for type 1 diabetes, but he did express excitement at its implications.

Christophe Benoist, M.D., Professor of Microbiology and Immunobiology at Harvard Medical School

Two of the talks focused on halting the progression of type 1 diabetes after antibodies are first detected. Christophe Benoist, M.D., professor of Microbiology and Immunobiology at Harvard Medical School, (who spoke on behalf of Diane Mathis, Ph.D., also a professor in the same department) discussed a molecule called I-BET that, when used as a treatment in animals during pre-diabetes or in the early stages of clinical type 1 diabetes, seemed to slow the progression of the disease.

Jay S. Skyler, M.D., M.A.C.P., Professor in the Division of Endocrinology, Diabetes and Metabolism at the University of Miami Miller School of Medicine, and the Chairman of the NIDDK Type 1 Diabetes TrialNet, talked about the diabetes intervention efforts applied during the earliest signs of type 1 diabetes.

A number of trials around the world aim to prevent the onset of diabetes altogether by targeting babies who are genetically at risk. Studies at this age mostly deal with nutritional supplementation or substitution. These studies aren’t close enough to completion to definitively announce results, but some--such as the one removing bovine insulin from cow’s milk formula--have shown some early signs of promise.

Dr. Skyler also reviewed a number of studies that involve subjects who already show some degree of autoimmunity. The majority of the studies he discussed did not show positive results--however, one study in which subjects take oral insulin pills at the onset of clinical disease is undergoing a second round as part of TrialNet due to suggestions of its efficacy.

Edward Damiano, Ph.D., Associate Professor of Biomedical Engineering, Boston University

One talk steered away from the more biological aspects of type 1 diabetes and into the realm of technology. Edward Damiano, Ph.D., Associate Professor of Biomedical Engineering at Boston University, spoke about his team’s efforts to produce an artificial pancreas.

He reviewed past, present and future studies that explore the feasibility of a closed-loop type 1 diabetes management system, involving a continuous glucose monitor, an insulin pump, and a glucagon pump all tethered to and controlled by a smartphone application, which is the “brain” of the system with the ability to ”make the decision to dose insulin and/or glucagon every five minutes,” he said. (Eventually, Dr. Damiano hopes the computer “brain” will reside on one of the pumps, removing the need for extra equipment.)

Over the course of three trials (with a fourth, the first out-patient trial, underway), “some people can really see their blood sugars essentially normalized,” he said. While not a cure, this type of closed-loop device would be a revolutionary step in diabetes self-management, allowing patients to essentially operate as though they had a fully-functioning pancreas.

This was the inaugural Joslin Symposium, organized by a team of Joslin researchers lead by Keith Blackwell, M.D., Ph.D., co-head of the Islet Cell & Regenerative Biology Section at Joslin Diabetes Center. It is planned for future symposia to cover rotating topics of importance in diabetes.

Page last updated: October 16, 2019