title: Hypoglycemia overrides amylin-mediated regulation of gastric emptying in rats.
abstract: Amylin, a 37-amino acid peptide hormone co-secreted with insulin, potently governs the rate of gastric emptying. Hypoglycemia, in the absence of agents such as amylin, is reported to accelerate gastric emptying. We asked whether hypoglycemia had a similar action on gastric emptying in the presence of amylin. In preliminary experiments using a phenol red gavage technique in fasted SD rats, we showed that insulin administration accelerated gastric emptying in a dosage-dependent manner. This acceleration was totally prevented by coadministration of glucose in dosages that prevented a change in plasma glucose, indicating that insulin per se did not affect gastric emptying. The effect on gastric emptying of hypoglycemia induced by a 5 mU/min insulin infusion (t = 5-90 min) was assessed in conscious rats continuously infused with amylin (50 pmol x kg-1 x min-1; t = -30 to 90 min). Gastric emptying was indicated by the appearance in plasma of label from 3-O-methyl-[3H]glucose gavaged at t = 0 min. Label appearance was markedly inhibited in rats preinfused with amylin (84% reduced vs. saline controls at t = 30 min), indicating amylin inhibition of gastric emptying. In amylin-treated rats that were subsequently infused with insulin, gavaged label abruptly appeared in plasma when plasma glucose had fallen to 2.1 +/- 0.1 mmol/l (at t approximately 45 min), consistent with a reversal by hypoglycemia of amylin's inhibition of gastric emptying. These data support the idea of a central "fail-safe" mechanism whereby hypoglycemia can override the slowing of gastric emptying by amylin.
authors.affiliation: Amylin Pharmaceuticals, San Diego, California 92121, USA.
authors.forename: B R
authors.initials: BR
authors.lastname: Gedulin
authors.forename: A A
authors.initials: AA
authors.lastname: Young
mesh_terms: D019325:3-O-Methylglucose / Q000097:blood / Q000378:metabolism; D000682:Amyloid / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005746:Gastric Emptying / Q000502:physiology*; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D007003:Hypoglycemia / Q000139:chemically induced / Q000503:physiopathology*; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D058228:Islet Amyloid Polypeptide; D008297:Male; D010637:Phenolsulfonphthalein; D051381:Rats; D014316:Tritium
chemical_list: D000682:Amyloid; D001786:Blood Glucose; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D014316:Tritium; D019325:3-O-Methylglucose; D010637:Phenolsulfonphthalein; D005947:Glucose