title: Differential incretin effects of GIP and GLP-1 on gastric emptying, appetite, and insulin-glucose homeostasis.
abstract: 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.
authors.affiliation: Department of Medicine, Karolinska Institutet Solna, Stockholm, Sweden.
authors.forename: T
authors.initials: T
authors.lastname: Edholm
authors.forename: M
authors.initials: M
authors.lastname: Degerblad
authors.forename: P
authors.initials: P
authors.lastname: Grybäck
authors.forename: L
authors.initials: L
authors.lastname: Hilsted
authors.forename: J J
authors.initials: JJ
authors.lastname: Holst
authors.forename: H
authors.initials: H
authors.lastname: Jacobsson
authors.forename: S
authors.initials: S
authors.lastname: Efendic
authors.forename: P T
authors.initials: PT
authors.lastname: Schmidt
authors.forename: P M
authors.initials: PM
authors.lastname: Hellström
mesh_terms: 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
chemical_list: 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