Streptozotocin causes pancreatic beta cell failure via early and sustained biochemical and cellular alterations

The morphological and biochemical changes that occur in the early phase of streptozotocin (STZ)-induced beta cell failure have not been characterized. The pancreas and plasma of rats treated with STZ were processed for morphological and biochemical parameters 124h and 4 weeks after STZ treatment. Marked reduction in body weight was observed as early as 3h post STZ treatment and hyperglycemia coupled with hypoinsulinaemia appeared in rats 1h after treatment with STZ. Hyperglycemia, hyperglucagonemia and hypoinsulinemia became permanent 24h after STZ treatment. The number of insulin-positive cells decreased significantly (p<0.05) at 24h after STZ treatment with a concomitant increase in the number of glucagon-immunoreactive cells. Electron microscopy showed coalescing of beta cell granules 18h after STZ treatment. A near to complete degranulation of beta cells settled at 21h after STZ administration. The pancreatic tissue and plasma levels of adrenaline and noradrenaline increased significantly (p<0.004: pancreatic tissue; p<0.04: plasma) 3h after STZ treatment and remained high after a reduction at 6h post STZ treatment. The pancreatic tissue and plasma levels of 5-HIAA decreased significantly (p<0.002 pancreatic tissue; p<0.04: plasma) 1h after STZ treatment and remained low after a reduction at 69h post STZ treatment. STZ elicited significant dose-dependent increases in insulin secretion from the isolated pancreas. The early changes in catecholamine level may be used in screening and follow-up studies on diabetes mellitus.