To examine the effects of long-term elevation of plasma gastric inhibitory polypeptide (GIP), the responses to parenteral (PA) or enteral (EA) alimentation were studied in consciousrats with duodenal and venous cannulae. A weight-maintaining liquid diet (84% as glucose, 16% as amino acids) was infused at a constant rate for 6 days by either route, and daily blood samples were taken. A subset of animals receiving PA also received porcine GIP with the infusate (PA plus GIP; plateau plasma immunoreactive GIP, IRGIP, 610 ± 120 pg/ml). With PA, plasma IRGIPdid not change from basal levels, whereas with EA IRGIP rose to virtual plateau levels (mean 530 ±110 pg/ml). In the steady state, plasma immunoreactive insulin (IRI) was significantly lower with EA (mean, 153 ± 5 μU/ml) than with PA (mean, 226 ± 15 μU/ml), which in turn was lower than with PA plus GIP (mean, 375 ± 23 μU/ml, P < 0.001 by ANOVA). A similar ranking of plasma glucose levels occurred in the steady state, with means of 113 ± 7 (EA), 126 ± 3 (PA), and 184 ± 9 (PA plus GIP) mg/dl (P < 0.001 by ANOVA). To assess the response to transient hyperglycemia in the steady state, an intravenous glucose bolus was given to each group on the fifth day. Peak plasma IRI levels did not differ among the three groups; however, the glucose disappearance rate was significantly slower with PA plus GIP compared with either EA or PA. Assuming that porcine GIP did not stimulate glucose production, this peptide appeared to induce hyperinsulinemia with insulin resistance during parenteral alimentation. The contrasting features of relatively low glucose and insulin levels during enteral alimentation associated with high levels of endogenous IRGIP in the blood suggest either (1) that the findings depend on variations of GIP or its actions in the different species, or (2) that mechanisms originating in the intestine act to preserve insulin sensitivity during absorption of nutrients from the gut under physiologic conditions.

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