Alternative splicing of G6PC2, the gene coding for the islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP), results in differential expression in human thymus and spleen compared with pancreas

Diabetologia
R S DograA Pugliese

Abstract

Autoimmunity to insulin, glutamic acid decarboxylase and the tyrosine-phosphatase-like protein IA-2 is associated with type 1 diabetes. The production of self-molecules in thymus and secondary lymphoid tissues is critical for self-tolerance; reduced levels may impair tolerance and predispose to autoimmunity, as shown for insulin. Alternative splicing causes differential expression of IA-2 gene (PTPRN) transcripts and IA-2 protein in human thymus and spleen compared with pancreas. IA-2 sequences not present in lymphoid tissues become autoimmune targets in type 1 diabetes. The beta cell molecule islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) is an autoantigen in the non-obese diabetic (NOD) mouse, a model of type 1 diabetes. IGRP is a candidate autoantigen in the human disease, but robust assays for IGRP autoantibodies and/or autoreactive T cells are not available. Both full-length and IGRP splice variants encoded by the G6PC2 gene are expressed in the pancreas. In this study we tested the hypothesis that IGRP splice variants could be differentially expressed in thymus and spleen compared with the pancreas. We evaluated the expression of G6PC2 transcripts in matched human thymus, spleen and pancreas...Continue Reading

References

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Citations

Apr 5, 2012·Cold Spring Harbor Perspectives in Medicine·Bart O Roep, Mark Peakman
Dec 24, 2009·Annals of Nutrition & Metabolism·F Y DemirciM I Kamboh
Jun 4, 2008·The Journal of Clinical Investigation·Wei-Min ChenRichard M Watanabe
May 22, 2010·Current Opinion in Endocrinology, Diabetes, and Obesity·Aaron W Michels, Maki Nakayama
Jun 19, 2013·Current Opinion in Endocrinology, Diabetes, and Obesity·Menno van LummelBart O Roep
May 1, 2006·Expert Review of Clinical Immunology·Alberto Pugliese
Mar 25, 2008·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Irene JarchumTeresa P DiLorenzo
Apr 24, 2007·Diabetes Research and Clinical Practice·Yongsoo Park
Nov 28, 2012·Diabetic Medicine : a Journal of the British Diabetic Association·A Pugliese
Aug 8, 2006·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Fan YangXiao-Feng Yang
Dec 26, 2012·Biochimica Et Biophysica Acta·Paola MarcolongoAngelo Benedetti
May 12, 2016·Current Diabetes Reports·Rene J McLaughlinBart O Roep
May 17, 2017·Current Opinion in Endocrinology, Diabetes, and Obesity·Liping YuAndrea K Steck
Jun 28, 2011·Endocrine Reviews·Vedran BrezarRoberto Mallone
Aug 2, 2017·The Journal of Clinical Investigation·Alberto Pugliese

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