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Intravenous Glucose Administration in Fasting Rats Has Differential Effects on Acylated and Unacylated Ghrelin in the Portal and Systemic Circulation: A Comparison between Portal and Peripheral Concentrations in Anesthetized Rats

Division of Endocrinology (C.G., P.U., P.K., R.M.K., J.A.M.J.L.J., P.J.D.D., M.O.v.A., L.J.H., A.P.N.T., A.J.v.d.L.), Department of Internal Medicine, Erasmus Medical Centre, 3015 GE Rotterdam, The Netherlands; Division of Endocrinology and Metabolism (E.G.), Department of Internal Medicine, University of Turin, 10126 Turin, Italy; and Postgraduate School of Molecular Medicine (A.J.v.d.L.), 3000 Rotterdam CA, The Netherlands

Address all correspondence and requests for reprints to: Carlotta Gauna, M.D., Division of Endocrinology, Department of Internal Medicine, Room Ee542, Erasmus Medical Center, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands. E-mail: c.gauna{at}erasmusmc.nl; or carlotta.gauna{at}unito.it.

Ghrelin is produced by the gastrointestinal tract, and its systemic concentrations are mainly regulated by nutritional factors. Our aim was to investigate: 1) endogenous portal and systemic acylated and unacylated ghrelin levels (AG and UAG, respectively); 2) whether an iv glucose tolerance test (IVGTT) modifies AG and UAG; and 3) 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 to UAG were also measured. IVGTT suppressed both portal (P < 0.03) and peripheral (P < 0.05) UAG, whereas it only blunted prehepatic, 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% but unaffected by glucose. The AG to UAG ratio was higher in the portal than the systemic circulation, both in the saline (P < 0.004) and IVGTT (P < 0.0005) rats. In conclusion, this study shows that: 1) the ratio of AG to UAG is very low in the portal vein and decreases further in the systemic circulation; 2) IVGTT in anesthetized fasting rats inhibits UAG, whereas it only blunts prehepatic, but not systemic, AG; and 3) 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.