Dose-response for Glucagonostatic Effect of Amylin in Rats

Metabolism. 1997 Jan;46(1):67-70. doi: 10.1016/s0026-0495(97)90170-0.

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.

MeSH terms

  • Amyloid / administration & dosage
  • Amyloid / blood
  • Amyloid / pharmacology*
  • Animals
  • Arginine / administration & dosage
  • Arginine / pharmacology
  • Blood Glucose / analysis
  • Blood Pressure / physiology
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Glucagon / blood*
  • Infusions, Intravenous
  • Insulin / blood
  • Islet Amyloid Polypeptide
  • Lactates / blood
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors

Substances

  • Amyloid
  • Blood Glucose
  • Insulin
  • Islet Amyloid Polypeptide
  • Lactates
  • Glucagon
  • Arginine