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Journal of Endocrinology (1991) 131, 267-278       DOI: 10.1677/joe.0.1310267 © 1991 Society for Endocrinology This Article

Oral insulin in diabetic dogs

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M. Saffran, J. B. Field, J. Peña, R. H. Jones and Y. Okuda

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Similar articles in PubMed Bovine crystalline insulin, mixed with an absorption enhancer, was Alert me to new issues of the journal loaded by hand into gelatin capsules, which were then coated with Download to citation manager an azopolymer designed to deliver the insulin in the upper colon. In Citing Articles 34 experiments with 14 pancreatectomized mongrel dogs of both Citing Articles via HighWire sexes, the coated capsules were administered orally after a pre-dose Citing Articles via Google Scholar period of 1 h. The dogs had cannulae in the portal vein, hepatic vein Google Scholar and femoral artery and Doppler flow probes on the portal vein and Articles by Saffran, M. hepatic artery. Insulin and food were withdrawn the day before an Articles by Okuda, Y. experiment. Responses measured were plasma glucose, plasma Search for Related Content insulin, hepatic glucose production rate, hepatic plasma flow rate PubMed and plasma glucagon-like immunoactivity (GLI). Control PubMed Citation experiments, with capsules without insulin, produced small changes Articles by Saffran, M. from 'pre-dose' values. Insulin-containing capsules, without the Articles by Okuda, Y. azopolymer coating, resulted in some early changes consistent with upper gastrointestinal absorption. Single oral doses (66 to 400 nmol/kg) of insulin in completely coated capsules produced peaks of portal plasma insulin and transient decreases in plasma glucose, hepatic glucose production, hepatic plasma flow and plasma GLI. The changes usually began 1·5–2 h after administration of a single dose, and lasted for up to 3 h, but were not significantly related to the dose of insulin. Multiple oral doses of insulin, given at 1·5-h intervals, resulted in multiple peaks of plasma insulin, a continuing dose-dependent fall in plasma glucose to near-euglycaemia with the highest dose, and profound decreases in hepatic glucose production and plasma GLI. These data demonstrate that insulin absorbed from the gastrointestinal tract causes changes in glucose metabolism in the diabetic dog that are consistent with the action of insulin primarily on the liver and that repeated oral doses are necessary to correct the hyperglycaemia.

Journal of Endocrinology (1991) 131, 267–278

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