Fig. 2

Gut ghrelin increases hepatic glucose production by activating a gut-brain-liver neurocircuitry. a Schematic representation of the working hypothesis. Gut ghrelin was coinfused with tetracaine, which abolishes the ascending neuronal signal to the brain. A subgroup of rats was given MK-801, an NMDA receptor inhibitor, directly into the NTS. In another study, gut ghrelin was infused into rats with HVAG. b Experimental procedure and clamp protocol. Stereotaxic surgeries were conducted on day 1. A duodenal catheter or venous and arterial catheters were implanted on day 7. HVAG was performed immediately before the implantation of the duodenal and vascular catheters. c and d Gut ghrelin infusion decreased GIR and increased HGP. Rats that received tetracaine in the gut, MK-801 in the NTS or HVAG failed to respond to duodenal ghrelin to decrease the GIR and increase HGP. e Suppression of HGP during the clamp expressed as the percentage decrease from basal HGP. f Glucose uptake was unchanged in all groups. NTS, the nucleus of the solitary tract; HVAG, hepatic vagotomy; NMDA, N-methyl- D-aspartate; GIR, glucose infusion rate; HGP, hepatic glucose production. Values are shown as mean ± SEM. *P < 0.05, **P < 0.01, vs. all other groups. (n = 7 for saline or ghrelin treated group; n = 5 per group for all other groups)