BES2005 Oral Communications Oral Communication 1: Diabetes and metabolism (9 abstracts)
Department of Metabolic Medicine, Imperial College London, London, UK.
The gastrointestinal-derived hormone peptide YY (PYY) is released from intestinal L-cells post-prandially in proportion to calorie intake, and modulates food intake. Peripheral administration of PYY (3-36) reduces food intake and body weight in rodents and suppresses appetite and food intake in humans. PYY(3-36) is hypothesised to inhibit food intake via activation of the auto-inhibitory pre-synaptic neuropeptide Y (NPY) Y2 receptor (Y2R) present on arcuate (ARC) NPY neurons. We aimed to investigate the feeding effect of PYY(3-36) following blockade of ARC Y2R, using the specific receptor antagonist BIIE0246, in the rat. We found that pre-treatment with BIIE0246 (1 nmol) into the ARC attenuated the reduction in feeding observed following intraperitoneal injection of PYY(3-36)(7.5 nmol/kg) (0-1 h food intake: BIIE0246/ PYY(3-36): 3.8 plus/minus 0.4 g; vs. Vehicle/ PYY(3-36): 2.7 plus/minus 0.2 g; p<0.05). We found plasma PYY levels to be maximal at 120 minutes post-initiation of feeding. On investigation of the endogenous role of the Y2R, we found that ARC administration of BIIE0246 alone significantly increased feeding in satiated rats compared to vehicle-injected controls (0-1 h food intake: BIIE0246: 4.1 plus/minus 0.7 g; vs. vehicle: 1.7 plus/minus 0.7 g; p<0.05), suggesting that Y2R antagonism disinhibits the NPY neuron thus stimulating feeding in otherwise satiated rats. These studies suggest that the Y2R plays an important role in post-prandial satiety and provide further insight into the mechanisms of action of PYY(3-36).