J. D. Young

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.

Serum Gastrin in Patients with Peptic Ulceration

The fasting serum level of gastrin was determined by radioimmunoassay in 41 normal subjects, 27 patients with duodenal ulceration, 12 patients with gastric ulceration, and 8 patients following “complete” vagotomy. The patients with duodenal ulceration had significantly higher serum levels of gastrin (1·3 ± S.D. 0·7 ng./ml.) than normal subjects (0·4 ± S.D. 0·3 ng./ml.), patients with gastric ulceration (0·4 ± S.D. 0·4 ng./ml.), or post-vagotomy patients (0·15 ± S.D. 0·2 ng./ml.). The gastrin secretion in both normal subjects and patients with duodenal ulceration was responsive to protein ingestion, but a larger incremental secretion of gastrin occurred in the latter group. Hyperglycaemia significantly suppressed the serum level of gastrin in both groups. The patients with gastric ulceration had fasting and postprandial serum gastrin levels not significantly different from normal subjects.

The gastrointestinal stimulus to insulin release: II. A dual action of secretin

The insulin release after an oral glucose load is both earlier and greater than would be expected from the glycemic stimulus. This augmentation of insulin release has been attributed to humoral factors from the gut. It has been previously demonstrated that secretin is released very rapidly after oral glucose and postulated that it acts as an early trigger to insulin release. This effect would not explain the magnitude of the peak insulin response which occurs about 30 min after peak secretin levels. The present studies, however, demonstrate an additional action of secretin which may explain this. To further study the role of secretin in insulin release in normal subjects, two consecutive 20 min intravenous glucose infusions were administered 150 min apart with and without an intervening secretin infusion (10 U) given to approximate serum secretin levels seen after oral glucose ingestion. A highly significant (P<0.01) potentiation of the insulin response to the post-secretin glucose infusion was observed. This occurred both when secretin was given 7 min or 25 min before glucose. In the latter case, serum secretin was undetectable during the glucose infusion. These studies demonstrate that secretin potentiates the glycemic release of insulin. Despite the augmented insulin response, no consistent change in blood glucose variation was observed. This is consistent with the suggestion that the facilitated disposal of an alimentary glucose load is not dependent solely on enhanced insulin secretion. Secretin appears to have a dual role in insulin release, an early direct stimulation followed by a prolonged potentiation of the glycemic stimulus. The potentiating effect is of such magnitude to suggest that secretin is the dominant factor in the enteric component of insulin release after an oral glucose load.