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To study the direct effect of intestinal factors on hepatic extraction of insulin, an investigation was made into the extraction of insulin from isolated rat liver perfused with portal venous effluent (PVE) obtained from the isolated perfused rat intestine. Rat intestine was perfused with Krebs-Ringer bicarbonate medium for 45 min, and the PVE was collected from glucose-, lipid-, or NaCl-treated and untreated control intestines. The PVE, after adjustment of its glucose (180 mg/dl) and insulin (200 microU/ml) concentrations, was used as the perfusing medium for the liver of a different rat. The liver was perfused without recirculation with the PVE not containing insulin for 15 min and then perfused with the PVE containing insulin for the next 30 min. Insulin removal from liver perfused with PVE from lipid- or NaCl-treated intestine (52.6 +/- 5.4 or 46.6 +/- 4.1%) was similar to that from comparable controls (49.7 +/- 2.8 or 48.2 +/- 2.9%), respectively. However, that from glucose-treated intestine (39.7 +/- 6.2%) was significantly (P less than 0.01) lower than that from control intestine (51.1 +/- 2.5%). These results indicate that an intestinal factor secreted after glucose ingestion significantly reduces hepatic extraction of insulin and that at least a part of the incretin phenomenon is due to a decreased hepatic extraction of insulin after oral glucose administration.

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