Ghrelin is produced by the gastrointestinal tract and its systemic concentrations are mainly regulated by nutritional factors.

Our aim was to investigate: i) endogenous portal and systemic acylated- and unacylated- ghrelin levels (AG and UAG, respectively); ii) whether an intravenous glucose tolerance test (IVGTT) modifies AG and UAG; iii) whether the liver passage plays a role in regulating systemic AG and UAG. To elucidate this, we evaluated the effects of IVGTT or saline injection on endogenous portal and systemic concentrations of glucose, insulin, AG and UAG in anesthetized fasting rats. Hepatic extraction of insulin, AG and UAG, and the ratio of AG/UAG were also measured.

IVGTT suppressed both portal (p<0.03) and peripheral (p<0.05) UAG, whereas it only blunted pre-hepatic, but not peripheral, AG. During fasting, hepatic clearance of UAG was 11% and it was decreased to 8% by IVGTT. AG was cleared by the liver by 38%, unaffected by glucose. The AG/UAG ratio was higher in the portal than in the systemic circulation, both in the saline (p<0.004) and in the IVGTT (p<0.0005) rats.

In conclusion, this study shows that: i) the ratio of AG/UAG is very low in the portal vein and decreases further in the systemic circulation; ii) IVGTT in anesthetized fasting rats inhibits UAG, whereas it only blunts pre-hepatic, but not systemic, AG; iii) hepatic clearance of AG is much higher than that of UAG. Thus, our results suggest that peripheral AG metabolic regulation and action are mainly confined within the gastrointestinal tract.