According to new research at the University of Chicago, the causes of Type 1 diabetes focus on auto-immune response, in which the immune system shatters the islets of Langerhans, which help to control the amount of glucose in the body.
According to findings published in Cell Reports, the researchers used genetic tools to knock out a gene called Alox15 in mice that were genetically predisposed to developing type 1 diabetes. This gene produces an enzyme called 12/15-Lipoxygenase, which is known to produce inflammation in beta cells. Deleting the Alox15 gene in these mice preserved their amount of beta cells, reduced the number of immune T cells infiltrating the islets and prevented Type 1 diabetes from developing. These mice also showed increased expression of the gene that suppresses autoimmunity.
“The immune system doesn’t just decide one day that it’s going to attack your beta cells. Our thinking was that the beta cell itself has somehow fundamentally altered itself to invite that immunity,” said senior author Raghavendra Mirmira, MD, PhD, Professor of Medicine and Director of the Diabetes Translational Research Center at UChicago. “When we got rid of this gene, the beta cells no longer signalled to the immune system and the immune onslaught was completely suppressed. There is a complex dialogue between beta cells and immune cells, and if you intervene in that dialogue, you can prevent diabetes.”
The study also revealed that new medications could block the immune system from destroying beta cells and prevent Type 1 diabetes from developing in at-risk or early onset patients. The researchers tested a drug that inhibits the 12/15-Lipoxygenase enzyme on human beta cells and saw that the drug, called ML355, could interrupt the autoimmune response and prevent diabetes from developing. Ideally, it would be given to patients who are at high risk because of family history and show early signs of developing Type 1 diabetes, or shortly after diagnosis. Mirmira and his team are taking the first steps to start clinical trials to test a possible treatment using ML355.
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