Role of circulating somatostatin in regulation of gastric acid secretion, gastrin release, and islet cell function. Studies in healthy subjects and duodenal ulcer patients.

Abstract

A s bstract. Studies were designed (a) to determine whether somatostatin is released into the circulation after meals in sufficient amounts to regulate gastric or pancreatic islet function in humans and (b) to investigate the possible role of somatostatin in the pathogenesis of duodenal ulcer disease. Mean plasma somatostatin-like immunoreactivity (SLI) increased from 6.2±1.5 pg/ml to a peak level of 13.8±1.3 pg/ml in eight healthy subjects after a 1,440-cal steak meal (P < 0.005). When somatostatin-14 was infused intravenously, basal and foodstimulated gastric acid secretion and also basal and foodsimulated plasma insulin and glucagon concentrations were reduced significantly at mean plasma SLI concentrations within the range seen after a meal. Thus, the amount ofsomatostatin reaching the systemic circulation after a steak meal was sufficient to inhibit gastric acid secretion and islet cell function. On the other hand, basal and food-stimulated plasma gastrin concentrations were reduced by intravenous somatostatin only at plasma SLI concentrations that were several-fold greater than postprandial SLI concentrations.Although duodenal ulcer patients had significantly higher basal, food-stimulated, and peak pentagastrinstimulated gastric acid secretion rates than healthy controls, duodenal ulcer patients and controls had nearly identical basal and food-stimulated SLI concentrations. Moreover, food-stimulated gastric acid secretion and gastrin release were inhibited by intravenous somatostatin Receivedforpublication 2 November 1983 and in revisedform 29 March 1984. to the same extent in ulcer patients and controls. These studies suggest that duodenal ulcer patients release normal amounts of somatostatin into the circulation and that target cells controlling acid secretion and gastrin release are normally sensitive to somatostatin in these patients.

Circulating somatostatin. Physiological regulator of pancreatic function?

“…Our results closely agree with other reports showing a similar postprandial SLI increase (4,5,16). Gel-filtration chromatography performed in this laboratory, indicated that roughly 50% of the postprandial SLI corresponded to S-14 in the volunteers under study (15).…”

“…Endocrine action of S-14 via the systemic circulation is supported by several recent studies (4)(5)(6)16). Colturi and coworkers (5) and Holst's group (6) have both independently studied the effects oflow dose infusions of somatostatin on meal-stimulated gastric acid and pancreatic islet cell function.…”

“…Recently an inhibitory effect of somatostatin on fasting plasma insulin and glucagon levels has been demonstrated in man (4), when synthetic somatostatin-14 (S-14)' was infused at concentrations that produced a rise of plasma somatostatin levels comparable to physiological levels observed after a meal. Two further human studies showed that such physiological amounts of S-14 as reaching the systemic circulation after a meal was sufficient to inhibit gastric acid secretion (5,6). Taken as a whole, these studies suggest an hormonal role of S-14 on the gastrointestinal tract.…”

“…First, the human pancreas contains mainly S-14 (31). Second, as S-14 and S-28 exert similar inhibitory effects in man, infusion of [5][6][7][8][9][10][11][12][13][14] should therefore give qualitatively and probably also quantitatively valid results. Third, it is probably impossible to mimick the adjusted molar amounts of both forms of the peptide to test this hypothesis conclusively.…”

Inhibition of gastrin gene expression by somatostatin.

“…In addition to its localization in several digestive organs, including the stomach, intestine, biliary tree, and pancreas (4, 5), somatostatin-like immunoreactivity has been demonstrated in the retina (6) in close proximity to both a-and /3-islet cells (7), in the cardiac vagus (8), and in the glomerulus of the kidney (9). It has been suggested that circulating somatostatin may play a physiologic role in the stomach (10,11) and pancreas (12). However, due to its widespread distribution somatostatin is a likely candidate for a local paracrine role in the regulation of various endocrine and exocrine cells (13).…”