Friday, May 25, 2012

A new Target for diabetes treatment - Apolipoprotein A-IV improves glucose homeostasis by enhancing insulin secretion

New research from the University of Cincinnati (UC) points to the naturally produced protein apolipoprotein A-IV (apoA-IV) as a potential target for a new diabetes therapeutics.  Apolipoprotein A-IV (APO-IV) is secreted by the small intestine in response to fat absorption. ApoA-IV–treated isolated pancreatic islets had enhanced insulin secretion under conditions of high glucose but not of low glucose, suggesting a direct effect of apoA-IV to enhance glucose-stimulated insulin release. . Knockout of apoA-IV results in compromised insulin secretion and impaired glucose tolerance compared with WT mice. Challenging apoA-IV−/− mice with a high-fat diet led to fasting hyperglycemia and more severe glucose intolerance associated with defective insulin secretion than occurred in WT mice. Administration of exogenous apoA-IV to apoA-IV−/− mice improved glucose tolerance by enhancing insulin secretion in mice fed either chow or a high-fat diet. Finally, we demonstrate that exogenous apoA-IV injection decreases blood glucose levels and stimulates a transient increase in insulin secretion in KKAy diabetic mice. These results suggest that apoA-IV may provide a therapeutic target for the regulation of glucose-stimulated insulin secretion and treatment of diabetes.