Up-regulation of clusterin (sulfated glycoprotein-2) in pancreatic islet cells upon streptozotocin injection to rats

Clusterin is a heterodimeric glycoprotein which has been shown to play impo rtant roles in programmed cell death and/or in tissue reorganization not on ly during embryonic development but also in damaged tissues. Recently, we r eported the transient induction of clusterin in pancreatic endocrine cells during early developmental stages of islet formation. In the present study, we have investigated the expression of clusterin in pancreatic tissue of s treptozotocin-treated rats which were undergoing extensive islet tissue reo rganization due to degeneration of insulin beta cells, clusterin was found in endocrine cells identified as glucagon-secreting alpha cells at the peri phery of the islet. Using immunoelectron microscopy, clusterin-positive cel ls showed the typical ultrastructural features of pancreatic alpha cells. I n addition, colocalization of clusterin and glucagon in the same secretory granules was shown by double immunogold labeling. These results imply that clusterin is a secretory molecule having endocrine and/or paracrine actions in parallel with glucagon. Further, we noted that clusterin expression was increased in pancreatic alpha cells during the process of beta cell death upon streptozotocin injection. The increase was significant as early as 1-3 h after streptozotocin treatment prior to any morphological alteration of islet beta cell and any manifestation of hyperglycemia. The expression of c lusterin was steady-stately up-regulated during the process of islet reorga nization caused by streptozotocin-induced cytotoxic injury. Therefore, we s uggest that clusterin might be considered as a molecule induced by both emb ryonic development and drug-induced reorganization of the endocrine pancrea s. Since clusterin expression is up-regulated in alpha cells, but not in be ta cells undergoing degeneration, it may play a protective role against the cytotoxic insult.