Exosomes from Beta-Cells May Be Key to Type 1 Diabetes; Under Stress, These Exosomes, Loaded with Three Known Autoantigens and Decorated with Cytokine-Induced Immune Enhancers, Are Released at a High Rate

Type-1 diabetes is the rarest, but most aggressive, form of diabetes, usually affecting young children and adolescents. The patient’s own immune cells begin to attack the beta-cells in the pancreas that make insulin, eventually eliminating its production in the body. The immune cells target certain proteins inside the insulin-producing cells. However, it is unclear how this actually happens. EPFL (Ecole Polytechnique Fédérale de Lausanne) scientists have now discovered that the immune attack in type-1 diabetes may be triggered by the release of proteins from the pancreas itself, as well as the package they come in. The work, which has significant implications for therapy strategies, is published in Diabetes. The article is titled “Primary Human and Rat Beta Cells Release the Intracellular Autoantigens GAD65, IA-2 and Proinsulin in Exosomes Together with Cytokine-Induced Enhancers of Immunity.” Scientists from EPFL’s Institute of Bioengineering, led by Steinunn Baekkeskov, Ph.D., have now discovered that pancreatic beta cells actually secrete proteins that are targeted by the immune attack. But it’s not only the proteins that cause problems; the researchers found that it is also their packaging. That packaging comes in the form of small vesicles called exosomes, which are secreted by all cell types to distribute various molecules with different functions. But previous studies have shown that exosomes can also activate the immune system. Building on this, the EPFL researchers looked at exosomes from human and animal pancreatic beta cells. The results showed that rat and human pancreatic beta cells release three proteins (GAD65, IA-2, and proinsulin) known to be associated with type-1 diabetes, and are in fact used by clinicians to diagnose its onset in people.
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