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DRI Researchers Publish in Leading Peer-Reviewed Journals 



New Findings Support the Use of IL-2 Therapy in Patients with Type 1 Diabetes
 

Dr. Alberto Pugliese, professor of medicine, immunology and microbiology and head of the DRI’s Immunogenetics Program, and Dr. Thomas Malek, professor and vice-chair of microbiology and immunology at the UM’s Miller School of Medicine, have conducted studies showing that low doses of the protein Interleukin-2 (IL-2) can boost the levels of regulatory T-cells (Tregs), cells of the immune system that suppress autoimmunity. IL-2 is also critical for the function of effector cells, whose job is to remove pathogens or cancer cells. In fact, high doses of IL-2 have been used to stimulate effector cells in the treatment of various cancers. 

Because of the dual activity of IL-2, it was important for the researchers to establish a therapeutic dosing range that would stimulate the Tregs but not the effector cells. In their latest study, published in Diabetes, Drs. Pugliese and Malek discovered that Tregs respond to a 10-fold lower dose of IL-2, providing them with critical data for new therapeutic approaches. 

“Mother Nature has equipped the effector cells and the regulatory cells with different internal machinery to process the IL-2 signal, such that they respond in different dose ranges. This understanding allows us to design trials based on the administration of low doses of IL-2 that selectively stimulate the regulatory cells and should suppress autoimmunity. This kind of therapy is really immunoregulation, rather than immunosuppression, and we hope it could be a major therapeutic benefit for patients with type 1 diabetes,” said Dr. Pugliese.

 


Skyler Comments in JAMA
  

The results of a small study conducted by researchers in Germany showed preliminary evidence that high doses of oral insulin may prevent the onset of type 1 diabetes in high-risk children. The study, published in the Journal of the American Medical Association (JAMA), was accompanied by an editorial from Dr. Jay Skyler, DRI’s deputy director for Clinical Research and Academic Programs, in which he commented on the various therapies that have been tested in the hopes of preventing the destruction of insulin-producing cells.  

While this latest study demonstrated that “oral exposure to insulin can promote a protective regulatory T-cell response,” Dr. Skyler said that several questions still need to be addressed in a definitive trial. “It is now possible to identify children at increased risk for type 1 diabetes at birth. What is missing are interventions to arrest this process prior to irreversible damage to the pancreatic beta cell.”   


Study Sheds Light on How Diabetes Develops
 

Dr. Per-Olof Berggren, head of cell biology and signal transduction and Mary Lou Held Visiting Scientist at the DRI and director of the Rolf Luft Diabetes Center at Karolinska Institutet in Stockholm, Sweden, and Dr. Midhat Abdulreda, assistant professor of surgery at the DRI, and their teams have revealed new evidence on a mechanism that contributes to failure and death of the insulin-producing beta cells during development of diabetes. The study, conducted in rodent models, was published in Proceedings of the National Academy of Sciences (PNAS)

Ten years ago, the same team, led by Dr. Berggren and Dr. Lisa Juntti-Berggren, professor of endocrinology and a practicing diabetologist, discovered that apolipoprotein CIII (apoCIII) is elevated in the blood of type 1 diabetes patients which produces excessive activation of certain calcium channels in the beta cells, causing their failure to release insulin and eventual death. In this recent study, the researchers show that apoCIII is also involved in type 2 diabetes and that the effect of apoCIII can be prevented by blocking the affected calcium channels. This may guide new therapeutic interventions to prevent beta cell deterioration during disease progression in both type 1 and type 2 diabetes.

"This adds another piece to the puzzle of this multifaceted disease, diabetes. We hope to leverage this new information to help preserve beta cell mass in type 1 and type 2 diabetes," says Dr. Abdulreda.


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