The researchers next induced Type 2 diabetes in a different group of normal mice. Five days after the disease was induced, the scientists treated the animals daily for 30 days with the investigational drug, called CPSI-1306 by its manufacturer, Cytokine PharmaSciences Inc. Two doses of the drug, one dose 10 times stronger than the other based on body weight, were put in water and given to the mice by mouth.
After four weeks of treatment, the mice receiving both levels of the drug sustained blood sugar levels of below 200 milligrams per deciliter. Experts suggest that blood glucose after eating should remain below 180 milligrams per deciliter in people with diabetes. By comparison, the blood sugar levels in untreated diabetic mice exceeded 400 milligrams per deciliter.
"The blood sugar levels came down to very near normal in the treated mice," Satoskar said.
Similarly, levels of IL-6 and TNF-alpha were substantially lower in treated mice vs. untreated mice. Animals receiving the higher dose of the drug, 0.1 milligram per kilogram of body weight, showed the lowest levels of these proinflammatory cytokines.
Satoskar explained that the molecule in the drug binds to MIF in a way that allows it to strip MIF of its three-part structure, preventing MIF from become biologically active. MIF is always present in the body, but isn't considered problematic until excess amounts of it are produced and active. Though it might have some physiological role in normal amounts, blocking it or interfering with its activity does not appear to cause any side effects in animals, he said.
The researchers suspect MIF acts on adipocytes, the cells that make up fat tissue, because they also found that the mice lacking MIF showed significantly lower levels than normal diabetic mice of a hormone called resistin, which is produced by adipocytes and contributes to insulin resistance.
"Finding that mice without MIF have less resistin suggests that MIF might do its damage by acting on adipocytes and making them produce more inflammation," Satoskar said.
Because Type 2 diabetes is strongly associated with obesity, these cells also could be responsible for production of the inflammatory cytokines that were shown in this study to be elevated in mice and humans, he said.
He and colleagues next plan to test the investigational drug on mice that model obesity and typically develop Type 2 diabetes after eating a high-fat diet.
Source: Ohio State University