Fig. 5: Hepatic p53 mediates the gluconeogenic action of glucagon.

p53 levels in a THLE-2 cells treated with glucagon (n = 5); b THLE-2 cells treated with glucagon and OSMI-1 (n = 6). c Protein levels of p53, CREB, pCREB, and PCK1 (n = 4) and d PCK1 activity (n = 6) in THLE-2 cells treated with empty-siRNA or siRNA-p53, and then kept in KHH or KHH + glucagon. e Protein levels of p53, CREB, and pCREB in THLE-2 cells treated with forskolin 2 µM (n = 6). f Protein levels of CREB, pCREB, and PCK1 in THLE-2 cells treated with empty-siRNA or siRNA-p53, and then challenged with forskolin (n = 6). g Glucose levels in THLE-2 cells treated with empty-siRNA or siRNA-p53 incubated with or without forskolin (n = 5). h PCK1 levels in Hep3B starved cells in the presence or absence of glucagon (n = 6). i Protein levels of CREB, pCREB, and PCK1 in Hep3B cells treated with forskolin (n = 6). j Protein levels of PCK1 and k glucose levels in Hep3B cells transfected with empty plasmid or plasmid encoding p53 and then treated with forskolin (n = 6). l Blood glucose levels in p53 floxed mice injected with AAV8 expressing either GFP (n = 6 and 7) or Cre (n = 7 and 9) and then treated with saline or glucagon (200 µg kg⁻¹). m Blood glucose levels in p53 LKO mice and their control littermates treated with saline or glucagon (n = 6). n O-GlcNAcylation of p53 in WT mice treated with saline or glucagon (200 µg kg⁻¹) (n = 4). o Schematic representation of the role of p53 in glucagon-induced gluconeogenesis. Expression of GAPDH served as a loading control, and control values were normalized to 100%. Data were presented as mean ± standard error mean (SEM). * denotes P < 0.05, ** denotes P < 0.01, and *** denotes P < 0.001, determined by two-tailed Student’s t-test (e, g, i, k, and n) or one-way ANOVA followed by Bonferroni post hoc testing (a, b, c, d, f, j, l, and m). “n” denotes independent animals or cell culture wells. Source data are provided as a Source Data file.