Gastrin does not stimulate growth of the rat pancreas

Gastrin is thought to stimulate growth of the pancreas via gastrin/cholecystokinin (CCK)-B-type receptors. The aim of the present study was to examine the trophic response of the pancreas to exogenous gastrin or to hypergastrinemia of endogenous origin and to hypogastrinemia with or without concomitant hyperCCKemia.

Hypergastrinemia was induced in male Sprague-Dawley rats by continuous infusion of human Leu15-gastrin-17 (5 nmol/kg/h, subcutaneously), by removal of the acid-producing part of the stomach (fundectomy), or by treatment with omeprazole (400 mumol/ kg/day, orally). Hypogastrinemia was induced by antrectomy or by gastrectomy. HyperCCKemia was induced by pancreaticobiliary diversion (PBD). The rats were killed 10 days or 8 weeks after the operations or treatments. The concentrations of circulating gastrin and CCK were measured by radioimmunoassay. The pancreatic weight and DNA content were determined.

Gastrin infusion, omeprazole treatment, and fundectomy greatly increased the serum gastrin concentration. The resulting levels were very similar in the three groups and probably represent the maximum attainable physiologic serum gastrin concentration. Whereas gastrin infusion or omeprazole treatment (hypergastrinemia) and antrectomy (hypogastrinemia) were without effect on the weight and DNA content of the pancreas, gastrectomy (hypogastrinemia) and fundectomy (hypergastrinemia) increased the weight and DNA content. PBD (hyperCCKemia) greatly increased the weight and DNA content of the pancreas. PBD plus fundectomy, PBD plus gastrectomy, PBD plus antrectomy, and PBD plus omeprazole increased the weight and DNA content of the pancreas, as did PBD alone.

CCK is a physiologically important trophic stimulus for the rat pancreas, but gastrin is not. The increase in pancreatic weight and DNA content after fundectomy and gastrectomy cannot be explained by means of either gastrin or CCK.