Tritiated taurine handling by isolated rat pancreatic islets.
A gating of volume-sensitive anion channels may participate in the depolarization of the plasma membrane caused by high concentrations of D-glucose in insulin-producing B-cells of the endocrine pancreas. The efflux of tritiated taurine from prelabeled cells is currently used to assess changes in the activity of such channels. The handling of [1,2-3H]taurine by isolated rat pancreatic islets was therefore investigated. The net uptake of [1,2-3H]taurine was found to represent a concentration-, time-, and temperature-dependent process. It was progressively increased in the range of D-glucose concentrations between 2.8 and 8.3 mM, but no further increase was observed at 16.7 mM D-glucose. Over 15 min incubation, the efflux of radioactivity from prelabeled islets was inhibited by MK571 (1.0 mM). It was increased in response to hypoosmolarity both in the presence and absence of extracellular Na+. Whether in salt-balanced or Na+-deprived media, the efflux of radioactivity from prelabeled islets increased in response to a rise in D-glucose concentration from 2.8 to 5.6 or 8.3 mM, but decreased when the concentration of the hexose was further increased from 8.3 to 16.7 mM. In perifused islets, however, the radioactive efflux from prelabeled islets was inhibited, in a concentration- related manner, when islets first deprived of D-glucose for 45 min were then exposed to 2.8, 5.6, or 16.7 mM D-glucose. Likewise, in prelabeled and perifused islets first exposed for 45 min to 4.0 mM D-glucose, a later rise in hexose concentration to 8.3 mM failed to affect significantly effluent radioactivity, while an increase in hexose concentration from 4.0 to 16.7 mM inhibited the radioactive outflow. In these perifusion experiments, the rise in D-glucose concentration provoked the expected changes in insulin output. The findings obtained in islets examined immediately after preincubation in the presence of [1,2-3H]taurine are consistent with the presence of volume-sensitive anion channels in islet cells and with a gating of such channels in response to a rise in D-glucose concentration from 2.8 to 5.6-8.3 mM. However, the radioactive fractional outflow rate from prelabeled islets seems to reach its highest value at about 8.3 mM D-glucose, being unexpectedly decreased at a higher concentration (16.7 mM) of the hexose. In conclusion, the pleiotropic effects of D-glucose upon tritiated taurine outflow from prelabeled rat islets, which could conceivably be ascribed to differences in the handling of this amino sulfonic acid by distinct islet cell types, indicates that the present approach is far from optimal to characterize unambiguously the regulation by the hexose of volume-sensitive anion channel activity in insulin-producing islet cells.
Jijakli
Hassan
H
Laboratory of Experimental Hormonology, Brussels Free University, Route de Lennik 808, B-1070 Brussels, Belgium.
Zhang
Ying
Y
Sener
Abdullah
A
Malaisse
Willy J
WJ
D000818:Animals; D005260:Female; D005947:Glucose / Q000494:pharmacology; D007038:Hypotonic Solutions / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D011422:Propionates / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013654:Taurine / Q000493:pharmacokinetics*; D014316:Tritium / Q000493:pharmacokinetics
D007038:Hypotonic Solutions; D007328:Insulin; D011422:Propionates; D011804:Quinolines; D014316:Tritium; D013654:Taurine; C059141:verlukast; D005947:Glucose