Streptozotocin Causes Pancreatic Beta Cell Failure via Early and Sustained Biochemical and Cellular Alterations

Abstract

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 1-24 h and 4 weeks after STZ treatment. Marked reduction in body weight was observed as early as 3 h post STZ treatment and hyperglycemia coupled with hypoinsulinaemia appeared in rats 1 h after treatment with STZ. Hyperglycemia, hyperglucagonemia and hypoinsulinemia became permanent 24 h after STZ treatment. The number of insulin-positive cells decreased significantly (p<0.05) at 24 h after STZ treatment with a concomitant increase in the number of glucagon-immunoreactive cells. Electron microscopy showed coalescing of beta cell granules 18 h after STZ treatment. A near to complete degranulation of beta cells settled at 21 h after STZ administration. The pancreatic tissue and plasma levels of adrenaline and noradrenaline increased significantly (p<0.004: pancreatic tissue; p<0.04: plasma) 3 h after STZ treatment and remained high after a reduction at 6 h post STZ treatment. The pancreatic tissue and plasma levels of 5-HIAA decreased significantly (p<0.002 pancreatic tissue; p<0.04: plasma) 1 h after STZ treatment and remained low after a reduction at 6-9 h 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.