Involvement of endogenous glucagon-like peptide-1 in regulation of gastric motility and pancreatic endocrine secretion.
OBJECTIVE
To study the role of endogenous glucagon-like peptide-1 (GLP-1) on gastric emptying rates of a solid meal as well as postprandial hormone secretion and glucose disposal.


METHODS
In nine healthy subjects, gastric emptying of a 310-kcal radio-labelled solid meal and plasma concentrations of insulin, glucagon and glucose were measured during infusion of saline or the GLP-1 receptor antagonist exendin(9-39)amide (Ex(9-39)) at 300 pmol·kg(-1)·min(-1).


RESULTS
Ex(9-39) infusion had no effect on the total gastric emptying curve, but changed the intra-gastric distribution of the meal. During infusion of Ex(9-39), more content stayed in the upper stomach (79.1 ± 2.5% of total during Ex(9-39) compared to 66.6 ± 5.7% during saline at 5 min). During Ex(9-39) infusion, higher concentrations of plasma glucagon were measured both before (after 40 min of Ex(9-39) infusion the glucagon level was 15.1 ± 0.7 pmol·L(-1) compared to 5.4 ± 1.4 during saline) and after the meal, and postprandial GLP-1 levels increased. Basal insulin and glucose levels were not affected by Ex(9-39), but the postprandial rise of insulin and glucose enhanced during Ex(9-39).


CONCLUSIONS
Endogenous GLP-1 is involved in the regulation of gastric motility in relation to meal intake and also in the regulation of postprandial insulin and glucose levels. Furthermore, endogenous GLP-1 seems to tonically restrain glucagon secretion.
Department of Gastroenterology and Hepatology, Karolinska University Hospital, Stockholm, Sweden.
Anne-Barbara
AB
Witte
Per
P
Grybäck
Hans
H
Jacobsson
Erik
E
Näslund
Per Martin
PM
Hellström
Jens Juul
JJ
Holst
Linda
L
Hilsted
Peter Thelin
PT
Schmidt
D000328:Adult; D001786:Blood Glucose / Q000187:drug effects; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology*; D005934:Glucagon / Q000097:blood / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D006815:Hunger / Q000187:drug effects; D007328:Insulin / Q000097:blood; D008297:Male; D009325:Nausea; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D019894:Peptide YY / Q000097:blood; D019518:Postprandial Period; D012527:Satiation / Q000187:drug effects
D001786:Blood Glucose; D007328:Insulin; D010446:Peptide Fragments; D019894:Peptide YY; C083773:exendin (9-39); D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005947:Glucose