Effects of metabolic inhibition by sodium azide on stimulus-secretion coupling in B cells of human islets of Langerhans.
Sodium azide (NaN3), a reversible inhibitor of mitochondrial respiration, blocks glucose-induced electrical activity and insulin secretion in human pancreatic islet B cells. Here we show that brief (10-15 min) application followed by removal of 3 mM NaN3 results in transient overshoot of electrical activity and insulin secretion even at substimulatory levels of glucose (3-5 mM). In addition, application of NaN3, even at very low [Ca2+]o, reversibly increases cytosolic Ca2+ to levels usually associated with substantial insulin release. These results suggest that (i) metabolic inhibition may reset B cell stimulus-secretion coupling and (ii) a rise in free cytosolic Ca2+, by itself, is not sufficient to trigger insulin secretion.
Misler
S
S
Department of Medicine (Jewish Hospital), Washington University, Saint Louis, Missouri 63130.
Barnett
D W
DW
Falke
L C
LC
D001386:Azides / Q000494:pharmacology*; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D004594:Electrophysiology; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D019810:Sodium Azide
D001386:Azides; D019810:Sodium Azide; D003576:Electron Transport Complex IV; D005947:Glucose