title: Dose-response for glucagonostatic effect of amylin in rats.
abstract: Glucagon secretion from pancreatic alpha cells is inhibited by insulin from beta cells. Amylin is a partner hormone to insulin cosecreted in response to nutrient stimuli, which, like insulin, inhibits beta-cell secretion. We investigated whether amylin also inhibits alpha-cell secretion of glucagon in response to infused L-arginine. Rat amylin (1.2, 3.6, 12, 36, or 120 pmol/kg/min; calculated plasma concentration, 13, 47, 195, 713, and 2,950 pmol/L, respectively; n = 7, 8, 6, 4, and 7) or saline (n = 23) was infused into anesthetized male Harlan-Sprague-Dawley rats during hyperinsulinemic-euglycemic clamps, which were used to equalize the influences of glucose and insulin on glucagon secretion. Plasma glucose and insulin concentrations and mean arterial pressures were not different between amylin- and saline-treated rats during a 10-minute 2-mmol L-arginine infusion delivered during the clamps. Plasma glucagon measurements taken during and after the arginine challenge showed that compared with saline infusions, amylin administration dose-dependently suppressed the glucagon response to arginine by a maximum of 62% (incremental area under the curve [AUC] 0 to 60 minutes) with a plasma amylin EC50 of 18 pmol/L +/- 0.3 log units. These data indicate that amylin potently inhibits arginine-stimulated glucagon secretion.
authors.affiliation: Amylin Pharmaceuticals, San Diego, CA 92121, USA.
authors.forename: B R
authors.initials: BR
authors.lastname: Gedulin
authors.forename: T J
authors.initials: TJ
authors.lastname: Rink
authors.forename: A A
authors.initials: AA
authors.lastname: Young
mesh_terms: D000682:Amyloid / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005934:Glucagon / Q000097:blood*; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D058228:Islet Amyloid Polypeptide; D007773:Lactates / Q000097:blood; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D000682:Amyloid; D001786:Blood Glucose; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D007773:Lactates; D005934:Glucagon; D001120:Arginine