INFLUENCE OF GASTRIC-ACID ON CIRCULATING SOMATOSTATIN-14 AND SOMATOSTATIN-28 RELEASED AFTER INSULIN-INDUCED HYPOGLYCEMIA IN CONSCIOUS DOGS

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 < 0.001), and plasma S-28 increased by 7.2 +/- 0.9 fmol/ml (P < 0.01). Suppression of hypoglycemia-mediated gastric acid secretion after the administration of omeprazole or ranitidine inhibited elevations of 8-14 by 82 +/- 6% (P < 0.001) and 81 +/- 7% (P < 0.001), respectively, but had no effect on the rise of S-28. Atropine (50-mu-g/kg, iv), which also suppresses gastric acid secretion after insulin hypoglycemia, decreased S-14 by 59 +/- 3% (P < 0.01) without influencing S-28. Atropine given after omeprazole treatment, however, increased S-14 by 38.9 +/- 6.5 fmol/ml, a response that was greater than the S-14 levels observed after atropine (P < 0.001) or omeprazole (P < 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.