Recently, Terazono et al. isolated and characterized a cDNA from a regenerating rat pancreatic islet-derived library, designated REG (for regenerating gene) that was over expressed in regenerating islets and underexpressed when endogenous insulin secretion was suppressed. Others have identified Reg (also known as pancreatic stone polypeptide) in exocrine pancreas, suggesting that Reg may be a paracrine growth factor for B-cells and may play a role in the beta-cells response to injury. Type I diabetes is characterized by autoimmune destruction of pancreatic beta-cells, while type II diabetes is characterized by abnormalities in insulin secretion and insulin action, or with the possible augmented loss of insulin secretory capacity with aging. We hypothesize that the REG gene may be important in a-cell response to autoimmunity (Type I diabetes), beta-cell dysfunction (Type II diabetes) and in aging. It is hoped that these studies will further our understanding of how a-cells respond to injury. In addition to possible providing a new marker for progressive beta-cell dysfunction and injury in diabetes, these studies may pave the way for new therapeutic strategies that alter REG gene expression in pancreas for the prevention or treatment of diabetes. We plan to use molecular techniques to measure mRNA levels of REG in the pancreas of rodents during the normal aging process, and in rodent strains with genetic forms of type I diabetes (NOD mouse, BB rat), and type II diabetes (db/db mouse, fa/fa rat).