Figure 1

Pro-inflammatory cytokines inhibit gluconeogenic program. (a–c) Effect of LPS (30 mg kg⁻¹) administration on hepatic G6pase luciferase reporter activity (a) as well as mRNA amounts for gluconeogenic genes (b), and circulating blood glucose concentrations (c) in fasted mice (n=9 in each group; *P<0.05). (d–f) Effect of IL-1β (10 μg l⁻¹), TNFα (10 μg l⁻¹) and IL-6 (10 μg l⁻¹) on gluconeogenic gene expression including G6pase (d) and Pck1 (e), as well as glucose output (f) in cultured primary hepatocytes exposed to glucagon (20 nm) (*P<0.05). (g) Immunoblot showing effects of IL-1β (10 μg l⁻¹) and TNFα (10 μg l⁻¹) on glucagon (20 nm)-induced CRTC2 dephosphorylation in primary hepatocytes. (h) Effect of IL-1β (10 μg l⁻¹) and TNFα (10 μg l⁻¹) on CRTC2 occupancy over the G6pase promoter in hepatocytes exposed to glucagon (20 nm) (*P<0.05). (i, j) Effect of wild type and phosphorylation-defective S171,275A CRTC2 overexpression on glucagon (20 nm)-induced G6pase mRNA amounts (i) and glucose output (j) in primary hepatocytes exposed to IL-1β (10 μg l⁻¹) and TNFα (10 μg l⁻¹) (*P<0.05).