"In type 1 diabetes, the immune system infiltrates pancreatic islets and destroys insulin-producing beta cells. While infiltrating immune cells are traditionally considered to negatively impact beta cells, recent studies in non-obese diabetic (NOD) mice have suggested that immune cells can also contribute to preserving beta cells," says lead author Ercument Dirice, Ph.D., research fellow in the Kulkarni Lab in the Section on Islet Cell and Regenerative Biology at Joslin Diabetes Center .
This finding is strengthened by the observation by Joslin researchers who reported that members of the Center’s 50-Year Medalist Study, who have lived with type 1 diabetes for 50 years or more, retain some beta cells and produce insulin.
"The traditional view of type 1 diabetes was that immune cells killed all beta cells and people with the disease would have to take insulin for life. But we know that some beta cells do survive and secrete insulin even when the patients have had type 1 diabetes for 50 years," says senior author Rohit N. Kulkarni, M.D., Ph.D., Associate Professor of Medicine at Harvard Medical School and the principle investigator of the project at Joslin. In this study,
Joslin researchers were interested in learning exactly how immune cells could promote beta cell growth and identifying the type of cell and the mechanisms underlying this effect.
In a series of experiments, the researchers injected NOD mice with immune cells from the pancreatic islets of donor NOD mice and assessed their effects on beta cells. The immune cells tested included subtypes of B or T immune cells.
Dirice, the lead author of the study, found that it is T cells not B cells that are associated with beta cell proliferation. Mice that received B cells showed no difference in beta cell growth. Mice that received the T cell subtypes CD4+ and CD8+ showed an elevation in all markers of beta cell proliferation compared to mice that did not receive them. The researchers also found that beta cell growth happens after islets are infiltrated by immune cells and is independent of the effects of glucose and insulin.
Further experiments with cell cultures showed that CD4+ and CD8+ cells secrete inflammatory cytokines and chemokines (Interleukin 2, Interleukin 6, Interleukin 10, MIP-1α and RANTES), which together enhanced beta cell proliferation. This is the first study to report that this group of "soluble factors" is involved in promoting beta cell growth.
"This gives us new insights into what is happening in the pathology of type 1 diabetes. The immune cells we identified send signals which appear to protect and promote growth of beta cells. This opens up an exciting new area that scientists have thought about; now we have the hard data to substantiate it," says Dr. Kulkarni.
The next step is to investigate the effects of immune cells on human beta cell growth. The factors secreted from CD4+ and CD8+ cells are potential therapeutic candidates to enhance beta cell growth to prevent or delay the onset of type 1 diabetes.
"We need to learn more about the relationship of beta cell death and proliferation to determine if we can harness these soluble substances to encourage beta cell proliferation rather than destruction," says Dr. Kulkarni.
This study was funded by the Juvenile Diabetes Research Foundation, National Institutes of Health and the Turkish Diabetes, Obesity and Nutrition Association.
About Joslin Diabetes Center
Joslin Diabetes Center, based in Boston, Massachusetts, undertakes diabetes research, clinical care, education and health and wellness programs on a global scale. Joslin is dedicated to ensuring that people with diabetes live long, healthy lives and offers real progress in preventing and curing diabetes . Joslin is an independent, nonprofit institution affiliated with Harvard Medical School, and is recognized worldwide for driving innovative solutions in diabetes prevention, research, education, and care.
Our mission is to prevent, treat and cure diabetes. Our vision is a world free of diabetes and its complications. For more information, visit www.joslin.org
About Joslin Research
Joslin Research comprises the most comprehensive and productive effort in diabetes research under one roof anywhere in the world. With 30-plus faculty-level investigators, Joslin researchers focus on unraveling the biological, biochemical and genetic processes that underlie the development of type 1 and type 2 diabetes and related complications.
Joslin research is highly innovative and imaginative, employing the newest tools in genetics, genomics and proteomics to identify abnormalities that may play a role in the development of diabetes and its complications. Joslin Clinic patients, and others with diabetes, have the option of participating in clinical trials at Joslin to help translate basic research into treatment innovations. Joslin has one of the largest diabetes training programs in the world, educating 150 M.D. and Ph.D. researchers each year, many of whom go on to head diabetes initiatives at leading institutions all over the globe. For more information, visit www.joslinresearch.org.
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