methylatropine and glucagon-like-peptide-1-(7-36)amide

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.

Topics: Animals; Atropine Derivatives; Blood Glucose; Chlorisondamine; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Injections, Intravenous; Insulin; Insulin Secretion; Jugular Veins; Kinetics; Male; Parasympatholytics; Peptide Fragments; Portal Vein; Rats; Rats, Sprague-Dawley; Time Factors