Mononuclear Cytotoxicity and Proliferation Towards Glucose Stimulated Rodent Pancreatic Islet Cells

Abstract

Diabetes is due to an autoimmune cellular immunologic destruction of the pancreatic beta cells. By the use of a chromium release assay and a proliferation assay we have investigated the possible role of beta cell activity for this destruction. Results show that in vitro glucose stimulated pancreatic islet cells are subjects to a slight but significantly higher cellular immunologic destruction by mononuclear spleen cells than unstimulated islet cells. The functional dependency of the islet cell destruction must be a product of both a mononuclear cell dysfunction and a specific islet cell pattern. This is due to the fact that all combinations of mononuclear cells and islet cells from diabetes prone BB rats and non-diabetes prone WF rats tested against each other, results in functional dependent cytotoxicity, except for the assay in which both effector cells and target cells are of WF rat origin. Additional observations indicate, that the diabetes prone BB rat mononuclear cells need previous in vivo activation as only cells from diabetic individuals, and not normoglycemic ones, display the reaction in question. Functional dependent cytotoxicity is validated in an other IDDM animal model — the NOD mouse. NOD mononuclear cells towards the murine MIN-6 beta cell line results in increased cellular cytotoxicity when the latter is glucose stimulated. Also the proliferative response of BB rat mononuclear cells to whole islets tend to show function dependency.