Effects of intravenous glucagon-like peptide-1 on gastric emptying and intragastric distribution in healthy subjects: relationships with postprandial glycemic and insulinemic responses.
BACKGROUND
The inhibitory action of glucagon-like peptide-1 (GLP-1) on gastric emptying (GE) is likely to be important in mediating its effects on postprandial glycemia, appetite, and gastrointestinal symptoms.


OBJECTIVE
The objective of the study was to evaluate the effects of "low" and "high" doses of iv GLP-1 on GE, intragastric meal distribution, glycemia, insulinemia, and appetite.


METHODS
Ten healthy males were studied on 3 d. GE of a solid (ground beef)/liquid (glucose) meal, blood glucose, plasma insulin, glucagon and glucose-dependent insulinotropic peptide, appetite perceptions, and gastrointestinal symptoms were evaluated during iv infusion of: 1) GLP-1 at 0.3 pmol x kg(-1) x min(-1) (GLP-1 0.3); 2) GLP-1 at 0.9 pmol x kg(-1) x min(-1) (GLP-1 0.9); and 3) 0.9% saline.


RESULTS
GLP-1 0.3 and 0.9 slowed GE of solid (intragastric retention at t = 100 min; saline: 28 +/- 5%; GLP-1 0.3: 53 +/- 6%; GLP-1 0.9: 58 +/- 7%; P < 0.001) and liquid (time for 50% of the liquid to empty, saline: 28 +/- 2 min; GLP-1 0.3: 42 +/- 7 min; GLP-1 0.9: 50 +/- 9 min; P < 0.001). Both doses of GLP-1 induced gastroparesis in about half the cohort and increased meal retention in the distal stomach (P < 0.05). GLP-1 attenuated the rises in glucose, insulin, and glucose-dependent insulinotropic peptide (P < 0.05). There was an inverse relationship between blood glucose at t = 15 min and the time for 50% of the liquid to empty (r = -0.70, P < 0.001).


CONCLUSIONS
In healthy subjects exogenous GLP-1 increases meal retention in the distal stomach and, even when administered in a "low" dose, frequently induces "gastroparesis," and the effects of GLP-1 on postprandial glycemia are predictable on the basis of its effect on GE, supporting the concept that GE is a major target mechanism for the clinical use of incretin mimetics.
Little
Tanya J
TJ
Department of Medicine, University of Adelaide, Royal Adelaide Hospital, Adelaide, South Australia 5000, Australia.
Pilichiewicz
Amelia N
AN
Russo
Antonietta
A
Phillips
Liza
L
Jones
Karen L
KL
Nauck
Michael A
MA
Wishart
Judith
J
Horowitz
Michael
M
Feinle-Bisset
Christine
C
D000328:Adult; D001066:Appetite / Q000502:physiology; D001786:Blood Glucose / Q000378:metabolism*; D005746:Gastric Emptying / Q000187:drug effects*; D005749:Gastric Inhibitory Polypeptide / Q000097:blood; D005753:Gastric Mucosa / Q000378:metabolism*; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D006815:Hunger / Q000187:drug effects; D007275:Injections, Intravenous; D007328:Insulin / Q000097:blood*; D008297:Male; D019518:Postprandial Period / Q000187:drug effects*; D012528:Satiety Response / Q000187:drug effects; D013270:Stomach / Q000187:drug effects; D016896:Treatment Outcome
D001786:Blood Glucose; D007328:Insulin; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon