Calmodulin and pancreatic B-cell function.

Abstract

In September-October 1979, two independent reports indicated the presence of the calcium-dependent regulatory protein, calmodulin, in rat pancreatic islet extracts 34'39. The reported values for the islet content in calmodulin averaged 0.11 and 0.13 pmoles per islet. In one of these studies, it was demonstrated that calmodulin binds to a membrane-rich particulate fraction prepared from a rat islet homogenate and causes activation of adenylate cyclase in the same subcellular materiaP 9. Both the specific binding of ~25I-labelled calmodulin and the activation of adenylate cyclase were Ca2+-dependent processes 39. In the other study, the allegedly specific inhibitor of calmodulin, trifluoperazine, was found to inhibit glucose-stimulated insulin release, whilst failing to affect the oxidation of glucose by rat islets 34. These pilot observations thus documented the presence of calmodulin in islet cells and the capacity of calmodulin to affect the activity of a target enzymatic system in the islets, raising the view that calmodulin may be involved in stimulus-secretion coupling in the B-cell. Thereafter, from 1980 onwards, about 30 further publications and three reviews 28'3t'36 were devoted to the same topic. The knowledge gained from these further studies indicates that calmodulin may affect the activity of several enzymes in the islets. However the precise role played by calmodulin in the secretory process remains to be fully elucidated.