FIG. 4.

Glucose tolerance and glucose production in NO-treated mice and hepatocytes. A: Representative immunoblots of insulin-stimulated primary hepatocytes cocultured with LSECs from WT or VECKO mice in transwell systems. Primary hepatocytes and LSECs were cultured in transwell systems with or without L-NAME (1 mmol/L) for 18 h. Hepatocytes and LSECs were stimulated with insulin (Ins) (10 nmol/L) for indicated times (n = 4). B–E: Gluconeogenic gene expression in primary hepatocytes cultured with LSECs from WT or VECKO mice in transwell systems (n = 4). Intraperitoneal glucose (F) and insulin (G) tolerance in 8-week-old SD-fed C57Bl6 mice injected with DETA-NONOate (DETA) or vehicle 30 min prior (−30 min) to glucose or insulin (n = 5) injection. Liver G6pc protein (H) and gluconeogenic gene expression (I) in C57Bl6 mice after 30 min of DETA-NONOate (20 mg/kg body wt i.p.) or vehicle injection (n = 3). J: Gluconeogenic gene expression in primary hepatocytes treated with or without DETA-NONOate. Primary hepatocytes were stimulated with dexamethasone (DEX)/cAMP for 8 h. DETA-NONOate (2.5 mmol/L) and/or insulin (10 nmol/L) were added after 2 and 4 h of DEX/cAMP stimulation, respectively (n = 4). K: Glucose production in primary hepatocytes treated with or without DETA-NONOate. Primary hepatocytes stimulated with DEX/cAMP in glucose production buffer for 4 h were stimulated with insulin or insulin/DETA-NONOate (2.5 mmol/L) for an additional 6 h. (n = 4). *P < 0.05, **P < 0.01, ***P < 0.001 vs. vehicle or between indicated groups. G6Pase-α, glucose-6-phosphatase-α. (A high-quality color representation of this figure is available in the online issue.)