Novel Chemical Modification of Insulin as Diagnostic Marker for Diabetes

Insulin is a hormone that mitigates absorption of glucose from the bloodstream by muscle and fat tissues. Insulin insufficiency causes the toxic accumulation of glucose in blood in a condition called Type 1 or juvenile diabetes (T1D). Often diagnosed in children and young adults, T1D involves the progressive loss of insulin-producing islet cells of the pancreas. In T1D, the immune system – our defense against infectious microbes and potentially harmful foreign substances – mounts a misguided destruction of islet cells. Thus T1D is classified as an autoimmune disorder, where the immune system fails to recognize certain cells of the body as “self.” Patients afflicted with T1D need a lifelong treatment with insulin, and are most prone to suffer a host of debilitating and life-threatening complications ranging from heart disease, stroke, and kidney malfunction. The exact nature of autoimmunity in T1D is yet to be fully understood. We discovered that insulin undergoes a novel chemical modification called deamidation making it liable to be recognized as “non-self”. In diabetic mouse models, we found that animals produce antibodies that specifically cross-react with deamidated insulin. We thus recognize the potential of these abnormal antibodies as diagnostic markers and therapeutic targets for T1D.