Cyclic AMP raises cytosolic Ca²⁺ and promotes Ca²⁺ influx in a clonal pancreatic β-cell line (HIT T-15)

The effect on cytosolic Ca²⁺ concentration ([Ca²⁺]_i) of cAMP analogues and the adenylate cyclase-stimulating agents forskolin, isoproterenol and glucagon has been examined in an insulin-secreting β-cell line (HIT T-15) using fura 2. All these manipulations of the cAMP messenger system promoted a rise in [Ca²⁺]_i which was blocked by the Ca²⁺ channel antagonists verapamil and nifedipine or by removal of extracellular Ca²⁺. The action of the adenylate cyclase activator forskolin was glucose-dependent. The results suggest that cAMP elevates [Ca²⁺]_i in HIT cells by promoting Ca²⁺ entry through voltage-sensitive Ca²⁺ channels, not through mobilization of stored Ca²⁺. Activation of Ca²⁺ influx may be an important component of the mechanisms by which cAMP potentiates fuel-induced insulin release.