Biphasic effect of insulin on beta cell apoptosis depending on glucose deprivation

Insulin resistant states are associated with an increase in the beta cell mass and also high levels of circulating insulin. Ultimately the beta cells undergo a failure that leads to diabetes. At this stage, a question arises if those persistent high levels of circulating insulin may contribute to beta cell damage. To address this important issue, we submitted beta cells to a prolonged effect of increasing concentrations of insulin. We observed that a prolonged effect of high levels of insulin on the presence of serum (15–24 h) in glucose-deprived beta cells induced apoptosis. This apoptotic effect was both dose- and cycloheximide-dependent.