Neuropeptide Y and peptide YY, but not pancreatic polypeptide, substance P, cholecystokinin and gastric inhibitory polypeptide, inhibit the glucagon- and noradrenaline-dependent increase in glucose output in rat liver.
OBJECTIVE
The gastrointestinal peptides neuropeptide Y (NPY), peptide YY (PYY), pancreatic polypeptide (PP), substance P (SP), cholecystokinin (CCK) and gastric inhibitory polypeptide (GIP) are released into the portal vein mainly during the absorptive phase. Their direct actions and their hormone modulatory effects on liver carbohydrate metabolism were investigated.


METHODS
Isolated rat liver, single-pass-perfused via both the hepatic artery (120 cm H2O, 30% flow) and the portal vein (20 cm H2O, 70% flow) with a Krebs-Henseleit buffer containing 5 mM glucose, 2 mM lactate and 0.2 mM pyruvate, NPY (5 nM), PYY (5 nM), PP (5 nM), SP (100 nM), CCK (100 nM) and GIP (10 nM) was infused for 10 min via either vessel. In additional experiments, insulin (100 nM), glucagon (1 nM) or noradrenaline (1 microM) were applied for 5 min via the portal vein during a 20 min portovenous infusion of one of the peptides.


RESULTS
Under basal conditions, neither arterial nor portal NPY, PYY, PP, SP, CCK or GIP modified hepatic glucose and lactate metabolism. Also, none of the peptides enabled an action of portal insulin in the normally insulin-insensitive isolated perfused rat liver. NPY and PYY, but not PP, SP, CCK or GIP, inhibited the increase in glucose release by glucagon and noradrenaline. Under basal conditions, none of the peptides altered hepatic flow. Only portal NPY and PYY enhanced slightly the noradrenaline-dependent reduction of portal flow.


CONCLUSIONS
NPY, PYY, PP, SP, CCK and GIP do not act directly as regulators of basal hepatic carbohydrate metabolism. NPY and PYY act as signal factors of the absorptive phase function as antagonists of the postabsorptive glucose regulatory hormones glucagon and noradrenaline.
Lüers
C
C
Institut für Biochemie und Molekulare Zellbiologie, Georg August Universität, Göttingen, Germany.
Gardemann
A
A
Miura
H
H
Jungermann
K
K
D000818:Animals; D002766:Cholecystokinin / Q000494:pharmacology; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D007262:Infusions, Intravenous; D019344:Lactic Acid / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008102:Liver Circulation / Q000187:drug effects; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D010191:Pancreatic Polypeptide / Q000494:pharmacology; D019894:Peptide YY / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013373:Substance P / Q000494:pharmacology
D009478:Neuropeptide Y; D019894:Peptide YY; D013373:Substance P; D019344:Lactic Acid; D005749:Gastric Inhibitory Polypeptide; D010191:Pancreatic Polypeptide; D005934:Glucagon; D002766:Cholecystokinin; D005947:Glucose; D009638:Norepinephrine