Gramicidin D is a potent insulin secretagogue: dependence on extracellular calcium influx.
Gramicidin D, a sodium ionophore, was identified as a potent insulin secretagogue in the mouse beta-cell line, beta TC3. Gramicidin D stimulated insulin secretion by 3.2-fold relative to control cells incubated with vehicle alone. Using ion-specific fluorescent probes, gramicidin D (1 microM) increased the intracellular concentrations of Na+ ([Na+]i) and Ca2+ ([Ca2+]i). By contrast, no changes in pHi were detected in cells exposed to ionophore. The increase in [Ca2+]i was biphasic and characterized by an initial peak at 1-2 minutes followed by a sustained second phase. The addition of EGTA (2 mM) to the extracellular medium abolished gramicidin D-induced increase in [Ca2+]i and insulin secretion. These parameters were also profoundly inhibited by the L-type Ca(2+)-channel inhibitor, verapamil (20 microM). These findings suggest that insulin secretion induced from beta TC3 cells by gramicidin D is mediated via the promotion of Ca(2+)-influx.
Dibas
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Department of Biochemistry, University of North Texas Health Science Center at Fort Worth 76107-2699, USA.
Yorio
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T
Easom
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D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D004533:Egtazic Acid / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D006096:Gramicidin / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D014700:Verapamil / Q000494:pharmacology
D007328:Insulin; D006096:Gramicidin; D004533:Egtazic Acid; D014700:Verapamil; D002118:Calcium