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Identification of Tissue-Restricted Transcripts in Human Islets

Institute of Genetics and Biophysics Adriano Buzzati-Traverso, National Research Center (A.M., G.D.P., P.E.H.), Naples 80125, Italy; Department of General Surgery, Medical University of Gdansk (P.W.), Gdansk 80-210, Poland; and Departments of Medicine (A.M., F.M., K.H., P.E.H.), Pediatrics (R.J.W.), and Surgery (Z.L., P.W., E.L., M.A.H.), Columbia University Medical School, New York, New York 10032

Address all correspondence and requests for reprints to: Dr. Paul E. Harris, Department of Medicine BB 20-06, Columbia University College of Physicians and Surgeons, 650 West 168th Street, New York, New York 10032. E-mail: peh1{at}columbia.edu.

The purpose of our study was to identify transcripts specific for tissue-restricted, membrane-associated proteins in human islets that, in turn, might serve as markers of healthy or diseased islet cell masses. Using oligonucleotide chips, we obtained gene expression profiles of human islets for comparison with the profiles of exocrine pancreas, liver, and kidney tissue. As periislet presence of type 1 interferon is associated with the development of type 1 diabetes, the expression profile of human islets treated ex vivo with interferon-2ß (IFN2ß) was also determined. A set of genes encoding transmembrane- or membrane-associated proteins with novel islet-restricted expression was resolved by determining the intersection of the islet set with the complement of datasets obtained from other tissues. Under the influence of IFN2ß, the expression levels of transcripts for several of the identified gene products were up- or down-regulated. One of the islet-restricted gene products identified in this study, vesicular monoamine transporter type 2, was shown to bind [³H]dihydrotetrabenazine, a ligand with derivatives suitable for positron emission tomography imaging. We report here the first comparison of gene expression profiles of human islets with other tissues and the identification of a target molecule with possible use in determining islet cell masses.

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