Diabetes researchers at Saint Louis University have discovered a way to prevent the onset of Type I diabetes mellitus in diabetic mice. This strategy involves inhibiting the autoimmune processes that result in the destruction of the insulin-secreting pancreatic beta cells.
Type I diabetes is a life-long disease that results from insufficient production of the vital anabolic hormone insulin. In most cases of Type I diabetes mellitus, the body’s immune system destroys insulin-producing beta cells, and this insulin deficiency causes high blood sugar levels, also known as hyperglycemia. Treatments for the disease require daily injections of insulin.
Dr. Thomas Burris, chair of the university’s pharmacological and physiological science department, and his colleagues, have published their results in the journal Endocrinology. IN this paper, they report a procedure that could potentially prevent the onset of the disease rather than just treating the symptoms
“None of the animals on the treatment developed diabetes even when we started treatment after significant beta cell damage had already occurred,” Burris explained in a prepared statement. “We believe this type of treatment would slow the progression of type I diabetes in people or potentially even eliminate the need for insulin therapy.”
A group of immune cells known as lymphocytes come in two main forms: B lymphocytes, which secrete the antibodies that bind to foreign cells and neutralize them, and T cells, which recognize foreign substances and regulate the immune response. There are several different types of T lymphocytes, but for the purposes of this discussion, two specific subtypes of T lymphocytes seem to be responsible for the onset of Type I diabetes. T “helper cells” that have the CD4 protein on their surfaces, and T “cytotoxic “ cells have the CD8 protein on their cell surfaces seem to play a role in the onset of Type I diabetes, but a third subtype of T lymphocyte has remained a bit of an enigma for some time. This subtype of T lymphocytes is a subcategory of CD4 T cells and secretes a protein called “interleukin 17,” and is, therefore, known as TH17.
Dr. Burris and his collaborators from the Department of Molecular Therapeutics at the Scripps Research Institute have been examining TH17 cells for some time and they came upon a pair of nuclear receptors that play a crucial role in the development of TH17 cells. Could hamstringing the maturation of TH17 cells delay the onset of Type 1 diabetes mellitus?
Burris and others targeted these receptors by using drugs that bound to them and prevented them from working. This prevented the maturation of the TH17 T lymphocytes. When two nuclear receptors, Retinoid-related orphan receptors alpha (ROR-alpha) and Gamma-t (ROR-gamma-t) were inhibited, they prevented the autoimmune response that destroyed the beta cells.
To block these ROR alpha and gamma t receptors, Burris and others used a selective ROR alpha inhibitor and a gamma t inverse agonist called SR1001 that was developed by Dr. Burris. These drugs significantly reduced diabetes in the mice that were treated with it.
These findings show that TH17 cells play a significant role in the onset of Type I diabetes, and suggest that the use of drugs like these that target this cell type may offer a new treatment for the illness.
According to the American Diabetes Association, only 5% of people with diabetes have the Type I form of the disease, which was previously known as juvenile diabetes because it is usually diagnosed in children and young adults. The organization said that over one-third of all research they conduct is dedicated to projects relevant to type 1 diabetes.