Intrameal IP Exendin-9 (Ex-9) infusion blocks the satiating effect of exogenous GLP-1, but alone fails to increase meal size

Abstract

Brief, intrameal, hepatic portal vein or IP GLP-1 infusions selectively reduce spontaneous meal size in rats [Ruttimann et al., Endocrinology 150:1174, 2009]. Here we examined the physiological significance of endogenous GLP-1 for meal size by testing the effects of the GLP-1 receptor antagonist Ex-9 on spontaneous eating and on the satiating effect of exogenous GLP-1. Adult male rats (n = 15–16) equipped with IP catheters received remotely controlled infusions (2.5 min, 0.2 ml/min) beginning 2 min into the 2nd (Ex-9 alone) or 1st (Ex-9 + GLP-1) nocturnal meal. Infusions of 10 or 30 nmol/kg Ex-9 vs. vehicle (V) did not affect meal size (10 nmol/kg, V: 2.5 ± 0.3, Ex-9: 2.0 ± 0.3 g; 30 nmol/kg, V: 2.0 ± 0.2, Ex-9: 1.8 ± 0.2 g, mean ± SE, Ps > 0.05) and decreased rather than increased meal duration (10 nmol/kg, V: 14.9 ± 1.8, Ex-9: 9.5 ± 1.3 min; 30 nmol/kg, V: 11.9 ± 2.7, Ex-9: 4.6 ± 0.4 min, Ps < 0.05). Subsequent meals and cumulative food intake were not affected. Infusions of 30 nmol/kg Ex-9 abolished the satiating effect of 10 nmol/kg GLP-1, but again did not increase meal size by itself (V: 2.6 ± 0.2; Ex-9: 2.5 ± 0.2; GLP-1: 2.1 ± 0.2; Ex-9 + GLP-1: 2.8 ± 0.3 g; ΔV/GLP-1 > ΔEx-9/Ex-9 + GLP-1, P < 0.05). These data show that a dose of Ex-9 that is sufficient to block the satiating effect of exogenous GLP-1 fails to increase meal size when administered under comparable conditions alone. This questions the physiological relevance of endogenous GLP-1 for the control of meal size under the present conditions.