A greater plasma concentration of insulin after isoglycemic enteral than after parenteral administration of glucose is called the incretin effect. The primary mediator of this effect, gastric inhibitory polypeptide, may not account for the complete manifestation of this phenomenon. We evaluated other gastroenteric polypeptides with respect to a differential response to oral ingestion of glucose and intravenous administration of glucose at rates that achieved arterial plasma glucose concentrations matched to those from orally administered glucose. Gastrin, peptide histidine methionine, peptide YY, and neurotensin showed increases in plasma concentrations in response to oral ingestion of glucose but not to intravenous administration of glucose. Vasoactive intestinal polypeptide showed no increased concentration in response to either oral or intravenous administration of glucose. The differential responses to orally and intravenously administered glucose noted in the former gastroenteric polypeptides qualifies them as potential mediators of the incretin effect.
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