Portal GLP-1 administration in rats augments the insulin response to glucose via neuronal mechanisms.
The incretin glucagon-like peptide-1 (GLP-1)-(7---36) amide is an important factor in prandial glucose homeostasis. Findings that GLP-1 is rapidly inactivated led to the hypothesis that the target of GLP-1 is close to the site of release. To investigate whether the target tissue is located in the hepatoportal system, we administered GLP-1 with glucose into the portal vein of rats and compared this with peripheral GLP-1 administration (jugular vein) and studied the effects of blockers of the nervous system. Portal GLP-1 augmented the insulin response to a portal glucose bolus by 81% (P < 0.01) and markedly improved the glucose disposal rate (P < 0.05). Peripheral administration of GLP-1 produced a similar augmentation of the insulin response (88%) and of the glucose disposal rate. However, only the effect of portal GLP-1 on insulin secretion was blocked by the ganglionic blocker chlorisondamine. The data suggest that prandial beta-cell stimulation by GLP-1 is evoked via a neural reflex triggered in the hepatoportal system. Because absorbed nutrients and GLP-1 first appear in the portal system, this mechanism may constitute a major pathway of GLP-1 action during meals.
Balkan
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B
Novartis Institute for Biomedical Research, LSB 3517, Summit, New Jersey 07901, USA. bork.balkan@pharma.novartis.com
Li
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X
D000818:Animals; D001286:Atropine Derivatives / Q000008:administration & dosage / Q000494:pharmacology; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D002714:Chlorisondamine / Q000494:pharmacology; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D007275:Injections, Intravenous; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007601:Jugular Veins; D007700:Kinetics; D008297:Male; D010276:Parasympatholytics / Q000008:administration & dosage / Q000494:pharmacology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D011169:Portal Vein; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D001286:Atropine Derivatives; D001786:Blood Glucose; D007328:Insulin; D010276:Parasympatholytics; D010446:Peptide Fragments; C055453:glucagon-like peptide 1 (7-36)amide; D004763:Glucagon-Like Peptides; C006649:methylatropine; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D002714:Chlorisondamine