In the new study, Ozcan and colleagues show that XBP-1s regulates blood sugar in a second way: It causes the degradation of a protein, FoxO1, whose actions include increasing glucose output from the liver and stimulating feeding behavior in the brain. This degradation of FoxO1, the researchers show, is independent of XBP-1s' effect on the insulin signaling system, and by itself leads to a reduction in blood glucose levels and increased glucose tolerance (more rapid clearing of glucose from the blood).

"Activating XBP-1s could be another approach to type 2 diabetes, and could be very beneficial for type 1 diabetes, too," says Ozcan. "Even in mice with no insulin, increased expression of XBP-1s lowered the blood glucose level significantly. This suggests that approaches that activate XBP-1s in the liver of type 1 diabetics could control blood glucose levels, with potentially much less requirement for insulin."

Ozcan's lab is now seeking practical ways to activate XBP-1s that would lend themselves to clinical development. Currently the only treatment for type 1 diabetes is insulin, which requires injections and requires close monitoring to avoid hypoglycemia. Drugs are available for type 2 diabetes, but it remains difficult to control.

SOURCE Children's Hospital Boston