INHIBITION OF PHOSPHATASES AND INCREASED CA2+ CHANNEL ACTIVITY BY INOSITOL HEXAKISPHOSPHATE

Inositol hexakisphosphate (InsP(6)), the dominant inositol phosphate i n insulin-secreting pancreatic beta cells, inhibited the serine-threon ine protein phosphatases type 1, type 2A, and type 3 in a concentratio n-dependent manner. The activity of voltage-gated L-type calcium chann els is increased in cells treated with inhibitors of serine-threonine protein phosphatases. Thus, the increased calcium channel activity obt ained in the presence of InsP(6) might result from the inhibition of p hosphatase activity. Glucose elicited a transient increase in InsP(6) concentration, which indicates that this inositol polyphosphate may mo dulate calcium influx over the plasma membrane and serve as a signal i n the pancreatic beta cell stimulus-secretion coupling.