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 IV with either 1) 7 mg of a gastrin monoclonal antibody (mAb 28.2); 2) 12.5 μg/k,o 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, IV), followed in 2 h by a 1-h infusion of histamine (40 μg/kg/h, IV). 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.
- Monoclonal antibody
- Vagus nerve
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience