Glucagon antagonism has been reported as a new therapeutic approach to hyperglycaemia. As the 14-3-3 protein YWHAB has been identified as a regulator of the glucagon receptor (GCGR) by affinity purification and mass spectrometry, we examined the role of YWHAB in vivo. Ywhab knockout mice display impaired blood glucose homeostasis only under pyruvate stimulation. Deletion of Ywhab in mouse primary hepatocytes (MPHs) increases hepatocyte glucose production by magnifying the effect of glucagon. Mechanistic analysis indicates that YWHAB forms a phosphorylation-dependent complex with GCGR and directly interacts with forkhead box O1 (FOXO1). Together, these results reveal the inhibitory role of YWHAB in glucagon-mediated hepatic glucose production, which may be a potential target for the control of gluconeogenesis and associated metabolic diseases.
基金：
National Nature Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81570778, 81870603, 81500615]
通讯机构：[1]Shanghai Jiao Tong Univ Affiliated Peoples Hosp 6, Dept Endocrinol & Metab, Shanghai Clin Ctr Diabet,Shanghai Key Clin Ctr Me, Shanghai Diabet Inst,Shanghai Key Lab Diabet Mell, 600 Yishan Rd, Shanghai 200233, Peoples R China[*1]Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic Disease, 600 Yishan Road, Shanghai, 200233, China
推荐引用方式(GB/T 7714)：
Ji Linlin,Wang Qianqian,Liu Mengdan,et al.The 14-3-3 protein YWHAB inhibits glucagon-induced hepatic gluconeogenesis through interacting with the glucagon receptor and FOXO1[J].FEBS LETTERS.2021,595(9):1275-1288.doi:10.1002/1873-3468.14063.
APA：
Ji, Linlin,Wang, Qianqian,Liu, Mengdan,Zhu, Chaoyu,Xiao, Yuanyuan...&Wei, Li.(2021).The 14-3-3 protein YWHAB inhibits glucagon-induced hepatic gluconeogenesis through interacting with the glucagon receptor and FOXO1.FEBS LETTERS,595,(9)
MLA：
Ji, Linlin,et al."The 14-3-3 protein YWHAB inhibits glucagon-induced hepatic gluconeogenesis through interacting with the glucagon receptor and FOXO1".FEBS LETTERS 595..9(2021):1275-1288
