Influence of gastric acid on circulating somatostatin-14 and -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 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.
Department of Medicine, University of Toronto, Ontario, Canada.
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Greenberg
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Pokol-Daniel
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Fung
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D002850:Chromatography, Gel; D004285:Dogs; D005744:Gastric Acid / Q000502:physiology*; D007003:Hypoglycemia / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D007328:Insulin / Q000494:pharmacology*; D009853:Omeprazole / Q000494:pharmacology; D010191:Pancreatic Polypeptide / Q000097:blood / Q000378:metabolism; D011899:Ranitidine / Q000494:pharmacology; D013004:Somatostatin / Q000097:blood / Q000378:metabolism*; D053561:Somatostatin-28; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D013004:Somatostatin; D010191:Pancreatic Polypeptide; D053561:Somatostatin-28; D001285:Atropine; D011899:Ranitidine; D009853:Omeprazole