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Series GSE9006 Query DataSets for GSE9006
Status Public on Sep 12, 2007
Title Gene expression in PBMCs from children with diabetes
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Objective: We hypothesized that type 1 diabetes (T1D) is accompanied by changes in gene expression in peripheral blood mononuclear cells (PBMCs) due to dysregulation of adaptive and innate immunity, counterregulatory responses to immune dysregulation, insulin deficiency and hyperglycemia. Research Design and Methods: Microarray analysis was performed on PBMCs from 43 patients with newly diagnosed T1D, 12 patients with newly diagnosed type 2 diabetes (T2D) and 24 healthy controls. One and four month follow-up samples were obtained from 20 of the T1D patients.
Results: Microarray analysis identified 282 genes differing in expression between newlydiagnosed T1D patients and controls at a false discovery rate of 0.05. Changes in expression of interleukin-1β (IL1B), early growth response gene 3 (EGR3), and prostaglandin-endoperoxide
synthase 2 (PTGS2) resolved within four months of insulin therapy and were also observed in T2D suggesting that they resulted from hyperglycemia. With use of a knowledge base, 81/282 genes could be placed within a network of interrelated genes with predicted functions including apoptosis and cell proliferation. IL1B and the MYC oncogene were the most highly-connected genes in the network. IL1B was highly overexpressed in both T1D and T2D, whereas MYC was dysregulated only in T1D.
Conclusion: T1D and T2D likely share a final common pathway for beta cell dysfunction that includes secretion of interleukin-1β and prostaglandins by immune effector cells, exacerbating existing beta cell dysfunction, and causing further hyperglycemia. The results identify several targets for disease-modifying therapy of diabetes and potential biomarkers for monitoring treatment efficacy.
Keywords: Diabetes, microarray analysis, peripheral blood mononuclear cells
 
Overall design We obtained blood samples from 24 healthy volunteers, 43 newly diagnosed T1D patients and 12 newly diagnosed T2D patients. All study participants were between the ages of 2 and 18 years. We collected samples one and four months after diagnosis from the last 20 of the T1D patients. For each time point one sample did not pass quality control and was dropped from the analysis. Patients with T2D were distinguished from T1D on the basis of age, body habitus,
presence (11/12 patients) of acanthosis nigricans, family history of type 2 diabetes (11/12 patients), and absence of autoantibodies to insulin, IA-2, and GAD65. We allowed low titers of insulin antibodies in T2D patients (< 4 U/mL), which have been previously reported. All but two
of the T1D patients with positive anti-insulin antibodies were also positive for at least one additional autoantibody.
 
Contributor(s) Kaizer EC, Glaser CL, Chaussabel D, Banchereau J, Pascual V, White PC
Citation(s) 17595242
Submission date Sep 11, 2007
Last update date Nov 14, 2018
Contact name Ellen Grishman
E-mail(s) ellen.grishman@childrens.com
Organization name UTSW Medical Center
Street address 5323 Harry Hines Blvd
City Dallas
State/province TX
ZIP/Postal code 75390
Country USA
 
Platforms (2)
GPL96 [HG-U133A] Affymetrix Human Genome U133A Array
GPL97 [HG-U133B] Affymetrix Human Genome U133B Array
Samples (234)
GSM228562 PBMCs-Healthy-H122_Healthy
GSM228563 PBMCs-Healthy-H124_Healthy
GSM228564 PBMCs-Healthy-H125_Healthy
Relations
BioProject PRJNA102489

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Supplementary file Size Download File type/resource
GSE9006_RAW.tar 489.3 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table
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