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Abstract

Bone is the only tissue of the vertebrate body that contains a cell type, the osteoclast, whose only function is to destroy the host tissue. This does not occur at random but rather in the context of a well ordered physiological process called bone modeling during childhood and remodeling during adulthood. We hypothesized that this process requires a daily delivery of a large amount of energy to bone cells; a large body of clinical observations supports this hypothesis. Testing this hypothesis led us to reveal the bone endocrine nature of bone and to identify osteocalcin as an osteoblast-derived hormone affecting multiple aspects of energy metabolism. We will review during this lecture the functions and mode of action of osteocalcin and address its overall importance in the control of whole body glucose homeostasis. SESSION 1: GS MIXTE RESPIRATIONBitter taste receptors in the lung: a new pharmacological target? S Grassin-Delyle a a UPRES EA220, Hôpital Foch, Universit e Versailles Saint Quentin en Yvelines, Saint Quentin en Yvelines Bitter taste receptors (TAS2Rs) are known for long for their role in taste as sensors of the presence of toxic compounds in foods, but their unexpected expression in airways epithelium and smooth muscle cells or in peripheral blood leucocytes has been recently documented. This family of GPCRs includes about 25 members in humans and each subtype has a variable selectivity towards bitter compounds, some of them being restrictedly selective to a unique molecule and others responding to a wider range. More than a hundred molecules such as chloroquine, caffeine, strychnine, colchicine or erythromycin have thus been described as TAS2R agonists while TAS2R19, 41, 42, 45 and 60 are considered as orphans since no agonist has been identified. In the airways, the initial observation by Desphandes et al. (2010) described the relaxation of pre-contracted mouse trachea following exposure to chloroquine, denatonium, quinine or saccharine, which was suggested to be even more pronounced that the relaxation obtained with the reference relaxing agents b2 -adrenoreceptor agonists. Interestingly, an original intracellular signaling pathway in the response of airway smooth muscle cells to bitter-taste receptor agonists was proposed, involving the G-protein bc subunit and leading to a localized increase in intracellular calcium, which in turn causes membrane hyperpolarisation through an activation of large conductance potassium channels (BK Ca). In addition to these results in cell cultures or airways preparations, inhaled bitter tastants were shown effective in decreasing airway resistance in ovalbumin-sensitized mice, but very little is known in humans to date. However, transcriptome analysis revealed upregulation of TAS2R signaling in peripheral blood leucocytes from patients with severe asthma, as well as a correlation between clinical markers of asthma severity and TAS2R expression. Overall, these works suggest that bitter taste receptors may constitute a new pharmacological target for obstructive l...