Influence of gastric acid on circulating somatostatin-14 and -28 released after insulin-induced hypoglycemia in conscious dogs.

Abstract

Insulin hypoglycemia is a potent mechanism for somatostatin secretion into the circulation. Whether the associated increase in gastric acid mediates the rise of one or both principle molecular forms of somatostatin, somatostatin-14 (S-14) and somatostatin-28 (S-28), was examined in four conscious dogs. Somatostatin molecular forms were separated by gel filtration chromatography after extraction of acidified plasma on octadecyl silyl cartridges and quantified by RIA. Basal plasma levels of S-14 and S-28 were 3.4 +/- 0.2 and 4.1 +/- 0.6 fmol/ml, respectively. After hypoglycemia induced by insulin, plasma S-14 increased by 29.5 +/- 3.9 fmol/ml (P less than 0.001), and plasma S-28 increased by 7.2 +/- 0.9 fmol/ml (P less than 0.01). Suppression of hypoglycemia-mediated gastric acid secretion after the administration of omeprazole or ranitidine inhibited elevations of S-14 by 82 +/- 6% (P less than 0.001) and 81 +/- 7% (P less than 0.001), respectively, but had no effect on the rise of S-28. Atropine (50 micrograms/kg, iv), which also suppresses gastric acid secretion after insulin hypoglycemia, decreased S-14 by 59 +/- 3% (P less than 0.01) without influencing S-28. Atropine given after omeprazole treatment, however, increased S-14 levels observed after atropine (P less than 0.001) or omeprazole (P less than 0.001) alone and was equivalent to control levels. S-28 remained unaltered after atropine and omeprazole treatment. These results in conscious dogs indicate that after vagal stimulation induced by insulin hypoglycemia 1) both S-14 and S-28 are released into the circulation, but S-14 predominates; 2) gastric acid contributes directly to the stimulation of S-14, but not S-28, secretion; 3) muscarinic inhibitory mechanisms participate in the regulation of S-14 secretion, and this mechanism is amplified when vagally stimulated gastric acid secretion is suppressed; and 4) nonmuscarinic mechanisms mediate in part S-28 secretion. This study suggests the presence of a reciprocal functional relationship between gastric acid secretion and circulating S-14 that is mediated by vagal muscarinic mechanisms.

Nutrient and Peptide Regulation of Somatostatin-28 Secretion from Intestinal Cultures1

“…Moreover, differential effects of muscarinic pathways on S14 and S28 release have been reported in the dog, as acetylcholine stimulates S28 secretion, but causes inhibition of S14 (9,11). Similarly, muscarinic effects on SLI secretion from the isolated rat stomach are predominantly inhibitory (35,36).…”

“…Studies in vivo have elucidated an important role for the vagus nerves in regulating intestinal SLI release (8,9,11,34). Moreover, differential effects of muscarinic pathways on S14 and S28 release have been reported in the dog, as acetylcholine stimulates S28 secretion, but causes inhibition of S14 (9,11).…”

“…Such studies have largely been conducted using in vivo models and have relied heavily upon measurement of the circulating levels of somatostatin-like immunoreactivity (SLI) (9 -12, 16, 17). Independent mechanisms modulating the release of the two forms of somatostatin have been suggested by studies demonstrating differential neural regulation of S28 and S14 in the dog (9,11). However, data derived from in vivo models preclude definitive assessment of those factors (nutrients, peptide secretagogues, and neurotransmitters) that have direct effects at the cellular level.…”