CaV2.3 channel and PKClambda: new players in insulin secretion.

Insulin secretion is critically dependent on the proper function of a complex molecular network. Ca(V)2.3-knockout (Ca(V)2.3(-/-)) and PKClambda-knockout (PKClambda(-/-)) mouse models now suggest that these 2 players, the Ca(v)2.3 channel and PKClambda, are important constituents of this molecular network. Subsequent to glucose stimulation, insulin is released from the pancreatic beta cell in a biphasic pattern, i.e., a rapid initial phase followed by a slower, more sustained phase. Interestingly, Ca(2+) influx through the Ca(V)2.3 channel regulates only the second phase of insulin secretion. PKClambda seems to enter the beta cell nucleus and in turn modulates the expression of several genes critical for beta cell secretory function. Studies by Hashimoto et al. and Jing et al. in this issue of the JCI set out to answer the question of why numerous isoforms of proteins with similar functions are present in the beta cell. This is important, since it has been difficult to understand the modulatory and/or regulatory roles of different isoforms of proteins in defined subcellular compartments and at various times during the secretory process in both beta cell physiology and pathophysiology.