Cellular and subcellular localization of an Mr 64,000 protein autoantigen in insulin-dependent diabetes

Christie, M. R. and Pipeleers, D. G. and Lernmark, A. and Baekkeskov, S. (1990) Cellular and subcellular localization of an Mr 64,000 protein autoantigen in insulin-dependent diabetes. Journal of Biological Chemistry, 265 (1). pp. 376-381. ISSN 0021-9258

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Item Type:Article
Item Status:Live Archive

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 β and non-β cells and in selected rat tissues by immunoprecipitation of 35Smethionine-radiolabeled proteins with sera from diabetic patients or from healthy control individuals. When islet cell populations enriched in β or non-β cells were tested for the expression of the Mr 64,000 antigen, the protein was primarily observed in the β 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 β cell-restricted plasma membrane expression of the protein and support the hypothesis that this protein is a target antigen of β cell-specific autoimmunity in insulin-dependent diabetes.

Keywords:autoantigen, article, autoimmunity, cellular distribution, human, human cell, insulin dependent diabetes mellitus, pancreas islet beta cell, priority journal, tissue distribution, Animal, Animals, Newborn, Autoantigens, Cell Fractionation, Cell Membrane, Centrifugation, Density Gradient, Diabetes Mellitus, Insulin-Dependent, Immunosorbent Techniques, Islets of Langerhans, Male, Molecular Weight, Rats, Rats, Inbred Strains, Support, Non-U.S. Gov't, Support, U.S. Gov't, P.H.S., Tissue Distribution
Subjects:A Medicine and Dentistry > A100 Pre-clinical Medicine
Divisions:College of Science > School of Life Sciences
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ID Code:18169
Deposited On:10 Aug 2015 08:42

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