Effects of insulin on serum gastrin concentrations, gastric acid secretion and histamine mobilization in the rat

Small doses of insulin (<1.25 U/kg) caused hypoglycemia, stimulated gastric acid secretion slightly, activated gastric mucosal histidine decarboxylase moderately, and enhanced the pentagastrin‐induced activation of histidine decarboxylase. Large doses of insulin (>2.5 U/kg) caused marked hypoglycemia and hypergastrinemia. Moreover, it lowered gastric mucosal histamine concentration and greatly activated histidine decarboxylase. Gastric acid secretion was not stimulated. Pentagastrin‐stimulated acid secretion was blocked and histamine‐stimulated secretion slightly inhibited. Combined administration of insulin and glucose prevented the acid response (insulin dose 0.6 U/kg) and the activation of histidine decarboxylase but not the hypergastrinemia (2.5 U/kg). Paradoxically, combined treatment with insulin and glucose did not prevent pentagastrin from activating histidine decarboxylase. Glucose alone raised the serum gastrin concentration in both unoperated and vagotomized rats. The histidine decarboxylase activity was not raised. Glucose inhibited the pentagastrin‐induced release of histamine greatly but inhibited the pentagastrin‐induced enzyme activation only moderately. In antrectomized rats, large doses of insulin (>1.25 U/kg) had no effect on the serum gastrin concentration but stimulated gastric acid secretion in contrast to what was the case in unoperated rats. Glucose prevented the acid response to insulin. The gastric histidine decarboxylase was not activated by insulin following antrectomy. In vagally denervated rats, insulin (5 U/kg) increased the serum gastrin concentration slightly but did not raise the histidine decarboxylase activity. We interpret the results as follows: With small doses of insulin the gastric secretagogue effect is attributable mainly to vagal nerve stimulation evoked by the hypoglycemia. With large doses of insulin there is no acid response. The effects on the parietal cells of the ensuing hypergastrinemia are counteracted by an unknow mechanism, which however does not prevent gastrin from releasing gastric histamine and stimulating gastric histidine decarboxylase. The insulin‐induced release of gastrin is not elicited exclusively through vagal excitation by hypoglycemia, since insulin releases gastrin also after vagotomy and after glucose administration. The great enzyme‐activating effect of insulin is a consequence of gastrin release. In addition, however, insulin seems to enhance the responsiveness of the enzyme‐containing cells to gastrin. Insulin is a poor substitute for vagal excitation in that it exerts a number of actions which are unrelated to vagal excitation.