Time-dependent potentiation of the beta-cell is a Ca2+-independent phenomenon.

When isolated rat pancreatic islets are treated with 16.7 mM glucose, a time-dependent potentiation (TDP) of insulin release occurs that can be detected by subsequent treatment with 5() mM KCl. It has been thought that TDP by glucose is a Ca 2+ -dependent phenomenon and only occurs when exposure to glucose is carried out in the presence of Ca 2+ . In contrast to this we now demonstrate TDP under stringent Ca 2+ -free conditions (Ca 2+ -free buffer containing 1 mM EGTA). In fact, under these Ca 2+ -free conditions glucose caused an even stronger TDP than in the presence of Ca 2+ . TDP induced by glucose in the absence of extracellular Ca 2+ was unaffected by inhibitors of protein kinase C (PKC). However, cerulenin or tunicamycin, two inhibitors of protein acylation, eradicated TDP without affecting glucose metabolism. The TDP by glucose was not associated with an increase in the cytosolic free Ca 2+ concentration ([Ca 2+ ]i) during subsequent treatment with high K + . Exposure of islets to forskolin under Ca 2+ -free conditions did not cause TDP despite a large increase in the cellular cAMP levels. In conclusion, glucose alone induces TDP under stringent Ca 2+ -free conditions when [Ca 2+ ]i was significantly lowered. Protein acylation is implicated in the underlying mechanism of TDP.