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The effect of a physiologically relevant dose of pancreatic glucagon, 85 pmol/kg/hr, or saline on gastric acid secretion induced by modified sham feeding (chew and spit), was studied in 10 healthy volunteers. Gastric pH was held constant (pH 5.5) by intragastric titration. Glucagon infusion inhibited gastric acid secretion significantly, from 19.6±1.5 mmol H+ per hour during saline, to 10.4±1.4 mmol H+ per hour. Blood glucose increased during glucagon infusion and remained constant during saline infusion. Serum gastrin concentrations increased significantly by sham feeding, during saline as well as glucagon infusion, and no difference between the gastrin response during saline or glucagon infusion was found. Thus glucagon, in a physiologic dose, reduces vagally mediated acid secretion by a gastrin-independent mechanism.

The effect of intravenous infusion of glucagon in a dose of 85 pmol/kg/hr on submaximal pentagastrin-stimulated gastric acid secretion was studied in eight healthy volunteers. The study was repeated four times in each subject. By a glucose-insulin clamp technique blood glucose levels were kept constant during the studies at 5.0 mmol/liter (euglycemic clamp), 2.5 mmol/liter (hypoglycemic clamp), or 7.0 mmol/liter (hyperglycemic clamp) on three different days. Glucose and insulin were not infused during one control day study. During glucagon infusion, plasma glucagon levels increased but the level reached was lower during the hyperglycemic condition when compared to euglycemic and hypoglycemic conditions. Glucagon infusion inhibited gastric acid secretion during hyper- and euglycemic conditions but not during hypoglycemic conditions. Hyperglycemia caused a modest but significant inhibition of acid secretion. Serum gastrin concentrations were unaltered during glucagon infusion regardless of the level of blood glucose. The present observations indicate that the inhibitory effect of glucagon is independent of the glucagon-induced hyperglycemia, but the effect is lost when blood glucose is below a certain limit, suggesting that blood glucose may have a modulating effect on gastric acid secretion.

The effect of intravenous infusion of L-arginine on pentagastrin-stimulated gastric acid secretion was studied in 15 duodenal ulcer patients and 12 healthy subjects. In both groups L-arginine enhanced plasma concentrations of pancreatic glucagon equally and to levels similar to those seen after a protein-rich meal and inhibited the acid response in duodenal ulcer patients and in normal subjects. The study supports previous findings suggesting that pancreatic glucagon is a physiological inhibitor of gastric acid secretion but does not support the hypothesis of a defect in this inhibitory system in duodenal ulcer patients.

Duodenal ulcers can be produced in rats within 24 h by a single subcutaneous administration of cysteamine. To determine the role of gastric acid secretion in the pathogenesis of these ulcers, secretory and pathoanatomic studies were performed in chronic fistula rats after an ulcerogenic dose of cysteamine. A prolonged increase of acid secretion was seen after cysteamine, reaching fourfold the basal level after 5 h. The acid response lasted for 10 to 11 h. After vagotomy cysteamine-induced acid secretion was markedly reduced. Ulcer formation was prevented by vagotomy and by drainage of the gastric juice before it entered the duodenum. When a gastric acid output equivalent to that produced by the ulcerogenic dose of cysteamine was induced by repeated injections of pentagastrin, no mucosal changes were seen in the duodenum. These results indicate that, although some acid in the duodenum is required for ulcer formation, the hypersecretion of acid induced by cysteamine is not the only factor responsible for the development of duodenal ulcer.

Liver and serum zinc concentrations were investigated in 24 patients with alcoholic liver diseases, 22 patients with non-alcoholic liver diseases, and in 36 control subjects. The liver samples were obtained by percutaneous liver biopsies, and the ratio of hepatocytes to fibrous connective tissue was estimated. The liver zinc concentration was expressed in relation to the amount of hepatocytes, and the serum zinc concentration was calculated in relation to total, albumin-, and α2-macroglobulin-bound serum zinc. The results show that the liver zinc concentration was decreased in patients with alcoholic liver diseases (P < 0.01), in contrast to in patients with nonalcoholic liver diseases. Albumin-bound serum zinc was decreased in both groups (P < 0.001). The results indicate that alcoholic liver damage is associated with zinc deficiency.

The effect of intravenous infusion of glucagon (300 ng X kg−1X h−1), l-arginine (0.6 g X kg−1X h−1) and of saline on meal-stimulated gastric acid secretion was studied in six healthy volunteers. Infusion of glucagon and l-arginine enhanced plasma concentrations of pancreatic glucagon to 65-85 pmol/1, a level similar to that seen after a normal protein-rich meal. Both infusions significantly inhibited the acid response to the meal, most pronounced after l-arginine. The difference in acid inhibition could not be ascribed either to differences in plasma glucagon concentrations or to differences in serum gastrin concentrations. The study supports the concept that pancreatic glucagon is a physiological inhibitor of gastric acid secretion.

Gut glucagon-like immunoreactants (GLIs) are peptides of enteric origin, which have immunoreactivity in common with pancreatic glucagon. First reported in the intestine by Unger et al.1, GLIs are concentrated in the L-cells of the lower small intestine and the colon2. The primary structure of gut GLI-1, glicentin, a highly purified form of the major component of gut GLIs3, has recently been established. Glicentin contains 69 amino acid residues, has a molecular weight (Mr) of 8,128 (ref. 4) and contains the entire glucagon sequence4,5, thus establishing it as a member of the hormone family which includes glucagon, secretin, gastric inhibitory polypeptide and vasoactive intestinal polypeptide. Until now there have been insufficient amounts of pure glicentin to test its proposed role in the intestinal phase of the body's response to a meal6, but there is evidence which suggests that, like other members of the hormone family to which it belongs, glicentin can inhibit gastric acid secretion7–9. We confirm here that glicentin inhibits pentagastrin-stimulated acid secretion in the rat.