Inhibition of phosphatases and increased Ca²⁺ channel activity by inositol hexakisphosphate

Inositol hexakisphosphate (InsP₆), the dominant inositol phosphate in insulin-secreting pancreatic β cells, inhibited the serine-threonine protein phosphatases type 1, type 2A, and type 3 in a concentration-dependent manner. The activity of voltage-gated L-type calcium channels is increased in cells treated with inhibitors of serine-threonine protein phosphatases. Thus, the increased calcium channel activity obtained in the presence of InsP₆ might result from the inhibition of phosphatase activity. Glucose elicited a transient increase in InsP₆ concentration, which indicates that this inositol polyphosphate may modulate calcium influx over the plasma membrane and serve as a signal in the pancreatic β cell stimulus-secretion coupling.