Pramlintide, an amylin analog, selectively delays gastric emptying: potential role of vagal inhibition.
The amylin analog pramlintide delays gastric emptying in type I diabetics. The effects of multiple doses of pramlintide and the mechanism of action in non-amylin-deficient humans are unknown. We investigated the effects of pramlintide on gastrointestinal and colonic transit and on the plasma pancreatic polypeptide response to the meal in a parallel-group dose-response study with subjects randomized to placebo, or 30 or 60 microg (tid, sc) of pramlintide. Pramlintide delayed gastric emptying [half-time (t(1/2)): 112 min (SE 8.7 min), 169 min (SE 12 min), or 177 min (SE 25 min) after placebo or 30- or 60-microg pramlintide treatment, respectively; P = 0.033]. Pramlintide did not significantly affect small bowel or colonic transit. Pancreatic polypeptide concentrations in the first postprandial hour were lower with pramlintide than with placebo (P<0.01 for drug effect). An inverse correlation was observed between mean pancreatic polypeptide concentrations in the first postprandial hour and gastric emptying t(1/2) [Spearman correlation coefficient (R(s)) = 0.48; P = 0.044]. Pramlintide at 30 and 60 microg delays gastric emptying in healthy humans without affecting small bowel or colonic transit. Vagal inhibition is a potential mechanism of the effects of pramlintide on gastric emptying.
Samsom
M
M
Gastroenterology Research Unit, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
Szarka
L A
LA
Camilleri
M
M
Vella
A
A
Zinsmeister
A R
AR
Rizza
R A
RA
D000328:Adult; D000682:Amyloid / Q000494:pharmacology*; D001786:Blood Glucose / Q000032:analysis; D003106:Colon / Q000187:drug effects / Q000502:physiology; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects*; D005772:Gastrointestinal Transit / Q000187:drug effects; D006801:Humans; D007421:Intestine, Small / Q000187:drug effects / Q000502:physiology; D058228:Islet Amyloid Polypeptide; D008297:Male; D009433:Neural Inhibition / Q000502:physiology*; D010191:Pancreatic Polypeptide / Q000097:blood; D013997:Time Factors; D014630:Vagus Nerve / Q000502:physiology*
D000682:Amyloid; D001786:Blood Glucose; D058228:Islet Amyloid Polypeptide; D010191:Pancreatic Polypeptide; C105254:pramlintide