Synergistic effect of portal glucose and glucagon-like peptide-1 to lower systemic glucose and stimulate counter-regulatory hormones.
OBJECTIVE
Glucagon-like peptide-1 (GLP-1) is an insulinotropic hormone released from the gut in response to nutrients. Besides its well-established direct effect on pancreatic beta cells, GLP-1 may also act by activating sensors in the hepatoportal area. We therefore studied the impact of putative GLP-1 sensors in the splanchnic circulation.


METHODS
We infused GLP-1 into the portal vein of conscious dogs, while also infusing glucose intraportally or systemically. In the first experiment, we infused glucose intraportally, simulating portal glucose values obtained during a previous mixed-meal test, with or without co-infusion of intraportal GLP-1. In the second experiment, by infusing glucose systemically, with or without intraportal GLP-1, we investigated whether the effects of systemic glucose with or without portal GLP-1 infusion are similar to those observed in the first experiment.


RESULTS
Intraportal infusion of GLP-1 and glucose significantly raised peripheral GLP-1 levels, but did not produce an insulin response different from intraportal glucose alone. However, the resulting peripheral glycaemia was significantly lower compared to glucose infusion alone, and there were elevations in glucagon, cortisol and lactate. In contrast to the portal glucose infusions, there were no significant differences in glucose, insulin, glucagon, cortisol or lactate levels between systemic glucose infusion with or without GLP-1.


CONCLUSIONS
Portal GLP-1 and portal glucose, but not systemic glucose, can produce decreased peripheral glucose levels independently of hyperinsulinaemia. This suggests that portal GLP-1 and glucose receptors mediate insulin-independent changes in peripheral glycaemia and determine a strong counter-regulatory response, as reflected by changes in glucagon and cortisol.
Ionut
V
V
Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, 1333 San Pablo Street, Los Angeles, CA 90033, USA.
Hucking
K
K
Liberty
I F
IF
Bergman
R N
RN
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D004285:Dogs; D004357:Drug Synergism; D005934:Glucagon / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology*; D006854:Hydrocortisone / Q000097:blood; D007262:Infusions, Intravenous; D008297:Male; D023421:Models, Animal; D010446:Peptide Fragments / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D011169:Portal Vein; D011498:Protein Precursors / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*
D001786:Blood Glucose; D010446:Peptide Fragments; D011498:Protein Precursors; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005947:Glucose; D006854:Hydrocortisone