Diabetes treatment - potential new target

The online edition of Proceedings of the National Academy of Sciences reports that Cincinnati University (UC) researchers have discovered that apolipoprotein A-IV (apoA-IV), a naturally produced protein that has the ability to reduce blood sugar levels and enhance insulin secretion, could be a potential target for a new diabetes treatment. ApoA-IV is a protein secreted by the small intestine in response to fat absorption. According to earlier studies, apoA-IV is elevated in individuals following gastric bypass surgery, which is linked to improved symptoms in diabetes. Patrick Tso, PhD, professor in the UC Department of Pathology and Laboratory Medicine and his team discovered that mice that had an apoA-IV deficiency displayed an impaired glucose tolerance, meaning that their bodies failed to secret insulin to move glucose from their blood stream. When fed a continuously high-fat diet, the mice also developed diabetes. However, these mice displayed an improved insulin response to glucose despite their high-fat diet when injected with apoA-IV. The researchers also evaluated how diabetic mice responded to injected apoA-IV, and noted the same results as those that were fed a high-fed diet. According to Tso, the research demonstrates apoA-IVs similar behavior to incretin, a gastrointestinal hormone that prompts a higher insulin release after eating to prevent the onset of high blood glucose levels. Existing diabetes drugs have already utilized two of these well-known incretins, namely gastric inhibitory peptide (GIP) and glucagon-like peptide-1 (GLP-1). Tso comments: "The problem with both of these incretins is that they are short-lived - lasting only for minutes - and are quickly inactivated by an enzyme. They have also been linked to hypoglycemia, or low blood sugar, when administered when the body has a low glucose concentration. The challenge is to find something safer with a longer half-life." The apoA-IV protein has such long half-life, i.e. between seven and eight hours says Tso, and in vitro tests have demonstrated that the protein does not affect glucose levels when given at low glucose concentrations. To the contrary, it seems to normalize glucose levels. Cincinnati University has licensed the results to Apofore Corporation, who will conduct further studies of apoA-IV in humans to develop a new drug for diabetes.