Autoantibodies to the GLUT-2 glucose transporter of beta cells in insulin-dependent diabetes mellitus of recent onset.
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.
Inman
L R
LR
Department of Veterans Affairs Medical Center, Dallas, TX 75216.
McAllister
C T
CT
Chen
L
L
Hughes
S
S
Newgard
C B
CB
Kettman
J R
JR
Unger
R H
RH
Johnson
J H
JH
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
D001323:Autoantibodies; D007074:Immunoglobulin G; D008757:Methylglucosides; D009004:Monosaccharide Transport Proteins; D019325:3-O-Methylglucose