April 2004 - Dr. Miles Brennan of the Eleanor Roosevelt Institute at the University of Denver (ERI) and Dr. Ute Hochgeschwender of the Oklahoma Medical Research Foundation have patented a method of reducing insulin resistance that could lead to potential treatments for diabetes accompanying obesity.
Insulin is a hormone that prompts cells to store glucose, a natural sugar, while another hormone called glucagon has the opposite effect, prompting cells to release stored glucose into the bloodstream. In healthy individuals the two hormones achieve homeostasis, or balance. Type II diabetes occurs when the body becomes resistant to insulin, preventing it from storing glucose. Because melanocyte-stimulating hormone (MSH) causes the pancreas to secrete glucagon, MSH must be present for type II diabetes to develop. Obesity and high cholesterol are risk factors for the disease, which leads to high blood pressure, strokes, heart attacks, blindness, kidney failure and possible amputation of the lower extremities.
The new process, which is described in U.S. Patent #6,689,938, is for treatment of diabetes by administering an antagonist of MSH. The patent covers the use of a whole class of MSH antagonists, chemicals that either remove the hormone from the system or which block the action of MSH in the bloodstream.
"Because type II diabetes is essentially an insensitivity to insulin action, we can now circumvent this resistance by working on the glucagon half of the circuit," explains Brennan. "If you're insensitive to insulin, this approach may be able to bring you back into homeostasis by decreasing glucagon in the bloodstream."
Previous treatments for type II diabetes have focused on altering the amount of glucose in the bloodstream. Brennan and Hochgeschwender instead focused on regulating insulin resistance in genetically engineered mice by manipulating the amount of MSH in the bloodstream.
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"It's a whole new way of looking at diabetes," says Brennan. "People have been working on diabetes for years, and this is an entirely unexpected departure, both in understanding how diabetes works and also in treating it."
The patent also includes a method for identifying compounds useful for reducing insulin resistance in a patient with obesity or type II diabetes. That process works by administering a peptide compound with MSH to genetically engineered mice with a modified POMC gene, which is responsible for manufacturing MSH.
Administering different MSH compounds to mice with different modifications to the POMC gene stimulates the secretion of various other hormones, which can be further studied for their roles in insulin resistance. Another patent issued to the same inventors covers mice with a range of genetic modifications to the POMC gene. The genetic modifications create obese mice that, surprisingly, do not develop diabetes.
Source: University of Denver
