Differential incretin effects of GIP and GLP-1 on gastric emptying, appetite, and insulin-glucose homeostasis.
BACKGROUND
Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are major incretins with important effects on glucoregulatory functions. The aim of this study was to investigate effects of GIP and GLP-1 on gastric emptying and appetite after a mixed meal, and effects on insulin secretion and glucose disposal in humans.


METHODS
Randomized crossover single-blind study in 17 healthy volunteers receiving GIP (2 or 5 pmol kg(-1) min(-1), n = 8), GLP-1 (0.75 pmol kg(-1) min(-1), n = 9) or NaCl for 180 min with a radionuclide-labeled omelette and fruit punch (370 kcal). Outcome measures were gastric emptying rate, insulinogenic index, hunger, satiety, desire to eat, and prospective food consumption. Blood was analyzed for GIP, GLP-1, glucagon, C-peptide, peptide YY (PYY) and ghrelin.


RESULTS
Glucose-dependent insulinotropic polypeptide 2 and 5 pmol kg(-1) min(-1) decreased gastric half-emptying time from 128.5 ± 34.0 min in controls to 93.3 ± 6.3 and 85.2 ± 11.0 min (P < 0.05). Glucose-dependent insulinotropic polypeptide 5 pmol kg(-1) min(-1) decreased postprandial glucose (P < 0.001) and insulin (P < 0.05) with increased insulinogenic index. Glucose-dependent insulinotropic polypeptide had no effects on hunger, desire to eat, satiety or prospective consumption. Glucagon-like peptide-1 0.75 pmol kg(-1) min(-1) increased half-emptying time from 76.6 ± 7.6 min to 329.4 ± 71.6 (P < 0.01). Glucagon-like peptide-1 decreased plasma glucose and insulin (both P < 0.05-0.001), and increased insulinogenic index markedly. Hunger, desire to eat and prospective consumption were decreased (P < 0.05), and satiety borderline increased (P < 0.06).


CONCLUSIONS
The incretin effect of GIP and GLP-1 differs as GLP-1 exerts a strong glucoregulatory incretin through inhibition of gastric emptying, which GIP does not. Thus, GLP-1 as incretin mimetic may offer unique benefits in terms of weight loss in treatment of type 2 diabetes.
Edholm
T
T
Department of Medicine, Karolinska Institutet Solna, Stockholm, Sweden.
Degerblad
M
M
Grybäck
P
P
Hilsted
L
L
Holst
J J
JJ
Jacobsson
H
H
Efendic
S
S
Schmidt
P T
PT
Hellström
P M
PM
D000328:Adult; D001066:Appetite / Q000187:drug effects*; D001786:Blood Glucose / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects*; D005749:Gastric Inhibitory Polypeptide / Q000097:blood / Q000494:pharmacology*; D054439:Ghrelin / Q000097:blood; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000494:pharmacology*; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D006815:Hunger / Q000187:drug effects; D007118:Immunoassay; D054795:Incretins / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D008297:Male; D019894:Peptide YY / Q000097:blood; D012528:Satiety Response / Q000187:drug effects
D001786:Blood Glucose; D002096:C-Peptide; D054439:Ghrelin; D054795:Incretins; D007328:Insulin; D019894:Peptide YY; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon