title: Autoantibodies to the GLUT-2 glucose transporter of beta cells in insulin-dependent diabetes mellitus of recent onset.
abstract: Purified immunoglobulin G (IgG) from the serum of patients with insulin-dependent diabetes mellitus (IDDM) of recent onset inhibits high-Km uptake of 3-O-methyl-beta-D-glucose by rat pancreatic islets. To determine if the inhibition is the result of antibodies against GLUT-2, the high-Km glucose transporter of beta cells, we incubated IDDM sera with rat islet cells and with AtT-20ins cells transfected to express GLUT-2. IDDM sera inhibited glucose uptake in islet cells and in GLUT-2-expressing AtT-20ins cells but not in AtT-20ins cells transfected to express the low-Km isoform, GLUT-1. In 24 of 30 (77%) patients with newly diagnosed IDDM, IgG binding as measured by immunofluorescence and flow cytometry of the cells transfected to express GLUT-2 was > 2 standard deviations from the mean of the nondiabetic population; 29 of 31 (96%) of nondiabetic children were negative (P < 0.0001). Increased IgG binding could be removed by absorption with GLUT-2-expressing cells but not with GLUT-1-expressing cells. We conclude that most patients with IDDM of recent onset have autoantibodies to GLUT-2.
authors.affiliation: Department of Veterans Affairs Medical Center, Dallas, TX 75216.
authors.forename: L R
authors.initials: LR
authors.lastname: Inman
authors.forename: C T
authors.initials: CT
authors.lastname: McAllister
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.forename: S
authors.initials: S
authors.lastname: Hughes
authors.forename: C B
authors.initials: CB
authors.lastname: Newgard
authors.forename: J R
authors.initials: JR
authors.lastname: Kettman
authors.forename: R H
authors.initials: RH
authors.lastname: Unger
authors.forename: J H
authors.initials: JH
authors.lastname: Johnson
mesh_terms: D019325:3-O-Methylglucose; D000818:Animals; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood* / Q000302:isolation & purification; D002460:Cell Line; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood* / Q000302:isolation & purification; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D008757:Methylglucosides / Q000378:metabolism*; D009004:Monosaccharide Transport Proteins / Q000276:immunology* / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D008757:Methylglucosides; D009004:Monosaccharide Transport Proteins; D019325:3-O-Methylglucose