本文采用的英格恩产品: 体内转染
Inactivation of NF-κB2 (p52) Restrains Hepatic Glucagon Response via Preserving PDE4B Induction
Wen-Song Zhang 1 , An Pan 1 , Xu Zhang 1 , Ang Ying 1 , Gaoxiang Ma 1 2 , Bao-Lin Liu 1 , Lian-Wen Qi 3 4 , Qun Liu 5 , Ping Li 6
- 1 State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 210009, China.
- 2 Clinical Metabolomics Center, China Pharmaceutical University, Nanjing, 211198, China.
- 3 State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 210009, China. Qilw@cpu.edu.cn.
- 4 Clinical Metabolomics Center, China Pharmaceutical University, Nanjing, 211198, China. Qilw@cpu.edu.cn.
- 5 State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 210009, China. liuquncpu@126.com.
- 6 State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 210009, China. liping2004@126.com.
Abstract
Glucagon promotes hepatic gluconeogenesis and maintains whole-body glucose levels during fasting. The regulatory factors that are involved in fasting glucagon response are not well understood. Here we report a role of p52, a key activator of the noncanonical nuclear factor-kappaB signaling, in hepatic glucagon response. We show that p52 is activated in livers of HFD-fed and glucagon-challenged mice. Knockdown of p52 lowers glucagon-stimulated hyperglycemia, while p52 overexpression augments glucagon response. Mechanistically, p52 binds to phosphodiesterase 4B promoter to inhibit its transcription and promotes cAMP accumulation, thus augmenting the glucagon response through cAMP/PKA signaling. The anti-diabetic drug metformin and ginsenoside Rb1 lower blood glucose at least in part by inhibiting p52 activation. Our findings reveal that p52 mediates glucagon-triggered hepatic gluconeogenesis and suggests that pharmacological intervention to prevent p52 processing is a potential therapeutic strategy for diabetes.