Children’s Hospital Division of Endocrinology physician and researcher Umut Ozcan has demonstrated that the regulatory protein XBP-1s, when activated artificially in the liver, can normalize high blood sugar in both lean, insulin-deficient type 1 diabetic mice and obese, insulin-resistant type 2 diabetic mice.
This indicates that approaches aimed at increasing XBP-1s activity may benefit patients with either type of diabetes, and follows Ozcan’s previous work when he identified XBP-1s as a key to the body’s sensitivity to insulin, and showed its function to be impaired in the cases of obesity.
In this study, Ozcan and colleagues have shown XBP-1s to be capable of regulating blood sugar by degrading the FoxO1protein, which increases glucose output from the liver and stimulates feeding behavior in the brain.
This degradation is independent of XBP-1s’ effect on the insulin signaling system, and automatically leads to a blood glucose level reduction, and increased glucose tolerance.
Ozcan is now trying to find practical ways to activate XBP-1s which would lend themselves to clinical development.