GASTRIN PARTIALLY MEDIATES INSULIN-INDUCED ACID-SECRETION IN DOGS

A monoclonal antibody to gastrin was used to study the role of circula ting 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 mu g/kg atropine; 3) mAb 28.2 and atropine together; or 4) vehicl e (0.1% canine serum albumin in 0.15 M NaCl). Thirty minutes later, ac id secretion was stimulated by insulin (0.5 U/kg, IV), followed in 2 h by a 1-h infusion of histamine (40 mu g/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 hypogl ycemia (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, r espectively. Acid output after combined pretreatment (0.5 +/- 0.2 mmol /30 min) was not significantly different than after atropine alone. Hi stamine-stimulated acid output (15.8 +/- 2.5 mmol/30 min) was not sign ificantly reduced by any pretreatment. Insulin injection increased cir culating gastrin concentrations to 32 +/- 7 fmol/ml, which was not sig nificantly affected by atropine (39 +/- 9 fmol/ml). This study demonst rates that, in dogs, a significant part of insulin-stimulated acid sec retion is mediated by circulating gastrin.