To examine effects of streptozocin (STZ) on pancreatic islets in the absence of a functioning immune system, we examined isolated rat islets cultured for 96 h after a single 1-h exposure to STZ in vitro. In addition to an immediate and sustained suppression of insulin secretion, STZ also induced a progressive decline in insulin content per islet as well as in total islet tissue mass, characterized by a decrease in both islet number and volume. Viability studies show that STZ-induced cell death was also progressive and was not commensurate with loss of secretory function. Furthermore, mediatransfer experiments demonstrate that decline of tissue mass is not due to accumulation of metabolite or degradation products in the media. After 96 h in culture, untreated islets showed a marked insulinogenic capacity that was inhibited more than fourfold by the initial STZ treatment. Progressive loss of glucagon content per islet suggests that STZ causes disruption of islet morphological integrity. These progressive sequelae observed in vitro indicate that several aspects of the time-delayed attack on the β-cell by STZ are independent of a functioning immune system.

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