Rapid Publications High-Glucose Stimulation of 64,000-/Wr Islet Cell Autoantigen Expression

This study examined the effect of various extracellular glucose concentrations on the expression of a previously described 64,000-/Wr islet cell autoantigen associated with insulin-dependent diabetes mellitus. The protein was precipitated from patient serums incubated with Triton X-100 lysates of [35S]methionine-labeled rat pancreatic islets that had been cultured in 5, 11, or 28 mM glucose for 6 h or 3 days. In both types of experiment, 28 mM glucose was the most efficient stimulator of 64,000-Mr autoantigen production. In contrast, the class I antigens of the major histocompatibility complex, precipitated by a rabbit polyclonal antiserum, were not influenced by differences in glucose concentrations. Our data indicate that expression of islet cell antigens may be increased during the course of hyperglycemia and suggest that the functional activity of islet cells influences their antigenicity. Diabetes 38:1326-28, 1989. Insulin-dependent diabetes mellitus (IDDM) is regardedas an autoimmune endocrine disease, characterized bylymphocytic infiltration of the islets and the formation ofautoantibodies (1). Serums of patients with new-onset IDDM usually, but not always, contain antibodies that rec-ognize a 64,000-/Wr protein of unknown function in detergent lysates of [35S]methionine-labeled islets of human or rat origin (2,3). Knowledge about the nature and production of the 64,000-/Wr antigen is limited. In this study, we examined the effects of various glucose concentrations on the expression in vitro of islet cell antigens identified from serums of patients Glucose 1 mM = 18 mg/d