The gastrointestinal stimulus to insulin release. I. Secretin.

The gastrointestinal stimulus to the release of insulin has been investigated in man by the use of a radioimmunoassay for secretin. Serum secretin levels rose rapidly after the oral ingestion of glucose or protein and preceded the elevation of serum insulin. An intravenous infusion of highly purified secretin caused a release of insulin when the serum secretin levels were within the physiological range. Infusion of hydrochloric acid into the duodenum caused an elevation of serum secretin and serum insulin levels in normal subjects. A similar response of secretin and insulin was seen after intravenous infusion of pentagastrin even when the acid stimulus to the duodenum was prevented. The latter observation suggests that pentagastrin (and probably gastrin) releases secretin by a direct humoral effect which is later fortified by the arrival of gastric acid in the duodenum. These studies suggest that secretin participates in the augmentation of insulin release after oral stimuli, and that a rapid sequence of humoral events takes place, gastrin releasing secretin and secretin releasing insulin. Subsequently secretin release would be augmented by a local stimulus in the duodenum and insulin release by the rising level of blood glucose or amino acids. This humoral system, which could also involve other gastrointestinal hormones, would provide a mechanism for facilitating the release of insulin to coincide with the onset of metabolite absorption.