Effects of metabolic inhibition by sodium azide on stimulus-secretion coupling in B cells of human islets of Langerhans

Abstract

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.