Gastrin partially mediates insulin-induced acid secretion in dogs.
A monoclonal antibody to gastrin was used to study the role of circulating gastrin in mediating insulin-stimulated acid output. On separate days, seven adult dogs with chronic gastric fistulas were pretreated i.v. with either 1) 7 mg of a gastrin monoclonal antibody (mAb 28.2); 2) 12.5 micrograms/kg atropine; 3) mAb 28.2 and atropine together; or 4) vehicle (0.1% canine serum albumin in 0.15 M NaCl). Thirty minutes later, acid secretion was stimulated by insulin (0.5 U/kg, i.v.), followed in 2 h by a 1-h infusion of histamine (40 micrograms/kg/h, i.v.). Acid output (mmol/15 min) in gastric effluent collected through the gastric fistula was determined by titration with 0.2 N NaOH to pH 7.0. Plasma gastrin was measured by radioimmunoassay. Plasma glucose was measured by a glucose oxidase method on an auto analyzer. Insulin induced a profound hypoglycemia (55 +/- 8 mg/dl) that coincided with a marked increase in acid output to 7.1 +/- 0.6 mmol/30 min by 45 min after injection. MAb 28.2 pretreatment and atropine pretreatment reduced insulin-stimulated acid outputs to 2.7 +/- 0.7 mmol/30 min and to 0.6 +/- 0.2 mmol/ 30 min, respectively. Acid output after combined pretreatment (0.5 +/- 0.2 mmol/30 min) was not significantly different than after atropine alone. Histamine-stimulated acid output (15.8 +/- 2.5 mmol/30 min) was not significantly reduced by any pretreatment. Insulin injection increased circulating gastrin concentrations to 32 +/- 7 fmol/ml, which was not significantly affected by atropine (39 +/- 9 fmol/ml). This study demonstrates that, in dogs, a significant part of insulin-stimulated acid secretion is mediated by circulating gastrin.
Kovacs
T O
TO
Research Service, Department of Veterans Affairs, West Los Angeles Medical Center, CA 90073, USA.
Lloyd
K C
KC
Walsh
J H
JH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D004285:Dogs; D005402:Fistula; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects*; D005755:Gastrins / Q000276:immunology / Q000502:physiology*; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D013270:Stomach / Q000601:surgery; D013997:Time Factors
D000911:Antibodies, Monoclonal; D005755:Gastrins; D007328:Insulin; D001285:Atropine