The glucagon-like peptide (GLP)-1 receptor is a promising target for the treatment of type 2 diabetes and obesity, and there is great interest in characterizing the pharmacology of the GLP-1 receptor and its ligands. In the present report, we have applied bioluminescence resonance energy transfer 2 assays to measure agonist-induced recruitment of ␤arrestins and G-protein-coupled receptor kinase (GRK) 2 to the GLP-1 receptor in addition to traditional measurements of second messenger generation. The peptide hormone oxyntomodulin is described in the literature as a full agonist on the glucagon and GLP-1 receptors. Surprisingly, despite being full agonists in GLP-1 receptor-mediated cAMP accumulation, oxyntomodulin and glucagon were observed to be partial agonists in recruiting ␤arrestins and GRK2 to the GLP-1 receptor. We suggest that oxyntomodulin and glucagon are biased ligands on the GLP-1 receptor.

Epstein-Barr virus (EBV) open reading frame BILF1encodes a seven trans-membrane (TM) G protein-coupled receptor that signals with high constitutive activity through Ga i Paulsen et al., 2005). In this paper, the transforming potential of BILF1 is investigated in vitro in a foci formation assay using retrovirally transduced NIH3T3 cells, as well as in vivo by using nude mice. BILF1 revealed a substantial transforming potential that was dependent on constitutive signaling, as a signaling-deficient mutant completely lost its ability to transform cells in vitro, and an intermediately active triple-mutated receptor possessed an intermediate transforming potential. Furthermore, BILF1 expression induced vascular endothelial growth factor secretion in a constitutively active manner. In nude mice, BILF1 promoted tumor formation in 90% of cases, ORF74 (from Kaposi's sarcoma-associated herpes virus) in 100% of cases, whereas the signaling-deficient receptor resulted in tumor establishment in 40% of cases. These data suggest that BILF1, when expressed during EBV infection, could indeed be involved in the pathogenesis of EBV-associated diseases and malignancies. Furthermore, the correlation between receptor activity and the ability to mediate cell transformation in vitro and tumor formation in vivo supports the idea that inverse agonists for BILF1 could inhibit cell transformation and be relevant therapeutic candidates.

This study aimed to evaluate the effect of hydrolysable tannin supplementation on morphology, cell proliferation and apoptosis in the intestine and liver of fattening boars. A total of 24 boars (Landrace × Large white) were assigned to four treatment groups: Control (fed commercial feed mixture) and three experimental groups fed the same diet supplemented with 1%, 2% and 3% of hydrolysable tannin-rich extract. Animals were housed individually with ad libitum access to feed and then slaughtered at 193 d of age and 122 ± 10 kg body weight. Diets supplemented with hydrolysable tannin affected the morphometric traits of the duodenum mucosa as reflected in increased villus height, villus perimeter and mucosal thickness. No effect was observed on other parts of the small intestine. In the large intestine, tannin supplementation reduced mitosis (in the caecum and descending colon) and apoptosis (in the caecum, ascending and descending colon). No detrimental effect of tannin supplementation on liver tissue was observed. The present findings suggest that supplementing boars with hydrolysable tannins at concentrations tested in this experiment has no unfavourable effects on intestinal morphology. On the contrary, it may alter cell debris production in the large intestine and thus reduce intestinal skatole production.

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