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Inactivation of NF-κB2 (p52) restrains hepatic glucagon response via preserving PDE4B induction

Author

Listed:
  • Wen-Song Zhang

    (China Pharmaceutical University)

  • An Pan

    (China Pharmaceutical University)

  • Xu Zhang

    (China Pharmaceutical University)

  • Ang Ying

    (China Pharmaceutical University)

  • Gaoxiang Ma

    (China Pharmaceutical University
    China Pharmaceutical University)

  • Bao-Lin Liu

    (China Pharmaceutical University)

  • Lian-Wen Qi

    (China Pharmaceutical University
    China Pharmaceutical University)

  • Qun Liu

    (China Pharmaceutical University)

  • Ping Li

    (China Pharmaceutical University)

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.

Suggested Citation

  • Wen-Song Zhang & An Pan & Xu Zhang & Ang Ying & Gaoxiang Ma & Bao-Lin Liu & Lian-Wen Qi & Qun Liu & Ping Li, 2019. "Inactivation of NF-κB2 (p52) restrains hepatic glucagon response via preserving PDE4B induction," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12351-x
    DOI: 10.1038/s41467-019-12351-x
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