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. 2009 Mar;150(3):1174-81.
doi: 10.1210/en.2008-1221. Epub 2008 Oct 23.

Intrameal hepatic portal and intraperitoneal infusions of glucagon-like peptide-1 reduce spontaneous meal size in the rat via different mechanisms

Elisabeth B Rüttimann  1 , Myrtha Arnold, Jacquelien J Hillebrand, Nori Geary, Wolfgang Langhans
Affiliations

Intrameal hepatic portal and intraperitoneal infusions of glucagon-like peptide-1 reduce spontaneous meal size in the rat via different mechanisms

Elisabeth B Rüttimann et al. Endocrinology. 2009 Mar.

Abstract

Peripheral administration of glucagon-like peptide (GLP)-1 reduces food intake in animals and humans, but the sites and mechanism of this effect and its physiological significance are not yet clear. To investigate these issues, we prepared rats with chronic catheters and infused GLP-1 (0.2 ml/min; 2.5 or 5.0 min) during the first spontaneous dark-phase meals. Infusions were remotely triggered 2-3 min after meal onset. Hepatic portal vein (HPV) infusion of 1.0 or 3.0 (but not 0.33) nmol/kg GLP-1 reduced the size of the ongoing meal compared with vehicle without affecting the subsequent intermeal interval, the size of subsequent meals, or cumulative food intake. In double-cannulated rats, HPV and vena cava infusions of 1.0 nmol/kg GLP-1 reduced meal size similarly. HPV GLP-1 infusions of 1.0 nmol/kg GLP-1 also reduced meal size similarly in rats with subdiaphragmatic vagal deafferentations and in sham-operated rats. Finally, HPV and ip infusions of 10 nmol/kg GLP-1 reduced meal size similarly in sham-operated rats, but only HPV GLP-1 reduced meal size in subdiaphragmatic vagal deafferentation rats. These data indicate that peripherally infused GLP-1 acutely and specifically reduces the size of ongoing meals in rats and that the satiating effect of ip, but not iv, GLP-1 requires vagal afferent signaling. The findings suggest that iv GLP-1 infusions do not inhibit eating via hepatic portal or hepatic GLP-1 receptors but may act directly on the brain.

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Figures

Figure 1
Figure 1
A, Intrameal HPV infusions of 1 or 3 nmol/kg GLP-1 reduced the size of the first spontaneous dark-phase meal compared with vehicle infusions (F3/29 = 9.19; P < 0.001). The duration of the after IMI (F3,21 = 2.08; P > 0.05) (B), and the second meal size (F3.22 = 1.55; P > 0.05) (C) were not significantly affected by GLP-1 infusions. Values are means ± sem of 11 (A) or 10 (B and C) rats. *, P < 0.05 vs. zero dose, Bonferroni-Holm test after significant ANOVA.
Figure 2
Figure 2
Intrameal VC and HPV infusions of 1 nmol/kg GLP-1 reduced the size of the first spontaneous dark-phase meal similarly. Values are means ± sem from 12 double-cannulated rats. *, P < 0.05 vs. zero dose, Bonferroni-Holm test after significant ANOVA.
Figure 3
Figure 3
Intrameal HPV infusions of 0.5 or 1.0 nmol/kg GLP-1 reduced the size of the first spontaneous dark-phase meal similarly in rats after SDA (n = 7) or sham surgery (n = 7). *, P < 0.05 vs. zero dose, Bonferroni-Holm test after significant ANOVA.
Figure 4
Figure 4
Intrameal ip infusion of 10 nmol/kg GLP-1 reduced the size of the first spontaneous dark-phase meal in sham-operated rats (n = 6), but not in rats with SDA (n = 9). In contrast, HPV infusions of this dose of GLP-1 similarly reduced meal size in both surgical groups. *, P < 0.05 vs. vehicle; +, P < 0.05 (vehicle − ip GLP-1) difference in sham-operated rats vs. (vehicle − ip GLP-1) difference in SDA rats; Bonferroni-Holm tests after significant ANOVA.
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