GCG and Insulin resistance: Our work has some limitations: (1) although we established global and liver-specific p52 knockdown mice model using siRNA and AAV-shRNA transfection technology, further validation will be required using liver-specific p52-knockout mice; (2) oral glucose tolerance was improved in p52 knockdown mice, suggesting a potential role for p52 in insulin resistance that will be characterized in future work; (3) whether or not NIK is involved in p100 cleavage to p52 stimulated by glucagon remains to be further characterized.