Evidence for a role of microfilaments in insulin release from purified beta-cells.

To determine if the failure of purified beta-cells to secrete insulin in response to a glucose stimulus results from the absence of a cytoskeletal response, the effects of cytochalasins D and B on glucose-induced insulin release were investigated. Glucose alone failed to stimulate insulin release whereas glucose in the presence of glucagon, theophylline, cytochalasin D or B markedly potentiated insulin release. Cytochalasin D potentiated insulin secretion in a dose-dependent manner, and the combination of theophylline and cytochalasin D resulted in an insulin secretory response no greater than that produced by either agent alone. Both glucagon and theophylline are believed to mediate their effects via cAMP, however, cytochalasin D did not affect beta-cell cAMP levels. These results suggest that the inability of purified beta-cells to release insulin may result from the absence of the necessary modulation of the state of the microfilaments.