We previously showed that glucose intolerance in LDKO mice is resolved by hepatic inactivation of the transcription factor FoxO1 (that is, LTKO mice)-even though the liver remains insensitive to insulin.
The findings showed an elevated level of leukocyte mTOR in the Impaired Glucose Tolerance (IGT) group and leukocyte FOXO-1 in the Impaired Fasting Glucose (IFG) and IGT groups compared to the control group.
By contrast, silencing of miR-21 increased the protein levels of FOXO1, subsequently leading to a decrease in insulin sensitivity and impaired glucose intolerance in C57BL/6 mice fed with high-fat diet for 4weeks.
Glucose intolerance and insulin resistance of Lrictor(KO) mice could be fully rescued by hepatic expression of activated Akt2 or dominant negative FoxO1.