Characterization of a kinesin-related gene ATSV, within the tuberous sclerosis locus (TSC1) candidate region on chromosome 9Q34 |
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Authors: | RA Furlong CY Zhou MA Ferguson-Smith NA Affara |
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Affiliation: | INSERM Unité 45, H?pital Ed. Herriot, Lyon, France. |
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Abstract: | Peptide YY (PYY) is produced in endocrine L cells primarily localized in the distal bowel. These open-type L cells make contact with the intestinal chyme which may thus affect their secretory activity. The aim of the present study was to examine a large variety of luminal compounds found in colonic contents for their potential as PYY-releasing factors, using the isolated vascularly perfused rat colon. The release of PYY into the portal effluent was measured by a specific RIA. Luminal administration of 5 mM glucose or 0.5% (w/v) starch for 30 min did not induce significant release of PYY. Oleic acid (10 and 100 mM) also did not significantly increase PYY secretion. A pharmacological concentration of glucose (250 mM) and a mixture of amino acids (total concentration 250 mM) both induced PYY secretion (200% of basal). Pectin, a poly-galacturonic acid, evoked dose-dependent secretion of PYY-like immunoreactivity over the range 0.1-0.5% (w/v). The maximal response was observed after infusion of 0.5% pectin which induced a prompt and sustained release of PYY (300% of basal). Galacturonic acid itself (5%) produced marked PYY secretion. Gum arabic (0.5%) induced a gradual increase in portal PYY concentration (maximal response 250% of the basal value) whereas cellulose (0.5%) did not elicit PYY secretion. Luminal n-butyrate over the range 0.5-5 mM produced a dose-dependent release of PYY (maximal response 300% of the basal value with 5 mM n-butyrate). Increasing the concentration of n-butyrate to 100 mM provoked a gradual decrease in PYY secretion. Propionate was a less potent stimulant than n-butyrate, and acetate did not increase PYY secretion above the basal value. At a concentration of 2 or 20 mM, taurocholate, cholate and deoxycholate brought about PYY secretion while hyodeoxycholate was without effect. In conclusion, glucose and amino acids may mediate PYY release but only when they are present at high supraphysiological concentrations in the colon while oleic acid does not produce any PYY secretion. Physiological concentrations of fibers (pectin, gum arabic), short-chain fatty acids (n-butyrate, propionate) and bile salts (taurocholate, cholate, deoxycholate) are all potent stimulants of PYY release. Whether the release of PYY by luminal factors is coupled to water and electrolyte transfer via a local/paracrine pathway remains an open question which requires additional work with the isolated vascularly perfused colon preparation. |
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