Researchers at the Children’s Hospital in Boston, led by Umut Ozcan, MD, have found a regulatory protein that lowers blood sugar when it is high due to either lack of insulin or a decreased sensitivity to insulin.
The functioning of the regulatory protein, called XBP-1s, is impaired in the presence of obesity and insulin resistance. When it was artificially activated in the livers of obese mice with type 2 diabetes, their blood sugar came down sharply.
XBP-1s also regulates blood sugar in another way, by causing the degradation of FoxO1. FoxO1 increases glucose output from the liver and stimulates feeding behavior in the brain. Therefore, degrading FoxO1 reduces blood glucose levels and increases glucose tolerance (faster clearance 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,” said Ozcan in a press release. “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 is now looking for ways to activate XBP-1s that might lead to development of a medicine for diabetes.
Children’s Hospital Boston press release