Abstract
Antibodies to an Mr 64,000 protein from human or rat islets have been detected at high frequency in newly diagnosed insulin-dependent diabetic patients. In this study, we show that the antigenic and amphiphilic properties of the rat islet Mr 64,000 protein resemble that of the human protein. We have analyzed the expression of the Mr 64,000 protein in populations of pancreatic beta and non-beta cells and in selected rat tissues by immunoprecipitation of [35S]methionine-radiolabeled proteins with sera from diabetic patients or from healthy control individuals. When islet cell populations enriched in beta or non-beta cells were tested for the expression of the Mr 64,000 antigen, the protein was primarily observed in the beta cells. On analyzing preparations of islets, liver, kidney, thyroid, adrenal, pituitary, spleen, and thymus, the protein could only be detected in islets. The protein was also characterized in terms of its subcellular localization by Percoll density gradient centrifugation and was recovered in a fraction enriched in the plasma membrane marker, 5'-nucleotidase. These results are consistent with a beta cell-restricted plasma membrane expression of the protein and support the hypothesis that this protein is a target antigen of beta cell-specific autoimmunity in insulin-dependent diabetes.
Highlights
Universiteit, Brussels, Belgium; and the Q?anting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada
The protein was characterized in terms of its subcellular localization by Percoll density gradient centrifugation and was recovered in a fraction enriched in the plasma membrane marker, 5’-nucleotidase
Immunoreactivity of the M, 64,000 Protein from Human and Rat Islets to Sera from Healthy and Diabetic IndividualsIn the absence of specific antisera raised to the diabetesassociated M, 64,000 protein antigen, our characterization of this protein has been dependent on the use of sera from diabetic patients
Summary
The protein was characterized in terms of its subcellular localization by Percoll density gradient centrifugation and was recovered in a fraction enriched in the plasma membrane marker, 5’-nucleotidase. These results are consistent with a ,!3 cell-restricted plasma membrane expression of the protein and support the hypothesis that this protein is a target antigen of fi cell-specific autoimmunity in insulin-dependent diabetes. Insulin-dependent diabetes displays features typical of organspecific autoimmunity including the presence of autoantibodies to both cell surface and cytoplasmic antigens of the pancreatic islet [4,5,6]; cell surface autoantigens have been re-
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