title: Reduction of the cytosolic calcium activity in clonal insulin-releasing cells exposed to glucose.
abstract: The cytosolic Ca2+ activity of insulin-releasing clonal cells (RINm5F) was studied with the intracellular fluorescent indicator quin-2. When the extracellular Ca2+ concentration was 1 mM, the basal cytosolic Ca2+ activity was 101 +/- 5 nM. Depolarization with 25 mM K+ increased this Ca2+ activity to at least 318 nM, an effect completely reversed by the voltage-dependent channel blocker D-600. In the presence of K+ alone these channels appeared to have a half-life of 6.7 +/- 0.8 min. In contrast to the action of K+, exposure of the RINm5F cells to 4 mM glucose resulted in a reduction of the cytosolic Ca2+ activity. This effect was observed during K+ depolarization but was more pronounced under basal conditions when it amounted to 20%. The data provide the first direct evidence that glucose can decrease the cytosolic Ca2+ activity in beta-cells. Unlike the case in normal beta-cells the glucose effect on the voltage-dependent Ca2+ channels in the RINm5F cells is apparently not sufficient to overcome the intracellular buffering of Ca2+. A defective depolarization is therefore a probable cause of the failing insulin secretion of RINm5F cells exposed to glucose.
mesh_terms: D007516:Adenoma, Islet Cell / Q000378:metabolism*; D000634:Aminoquinolines / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002999:Clone Cells / Q000187:drug effects / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism*; D005711:Gallopamil / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats
chemical_list: D000634:Aminoquinolines; D005711:Gallopamil; C035738:Quin2-acetoxymethyl ester; D005947:Glucose; D011188:Potassium; D002118:Calcium