Gene expression changes in human islets exposed to type 1 diabetic serum

Andrew M. Jackson, Mazhar A. Kanak, Ellen K. Grishman, Damien J. Chaussabel, Marlon F. Levy, Bashoo Naziruddin

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

A major obstacle to the success of islet cell transplantation as a standard treatment for labile type 1 diabetes mellitus is the immediate loss of up to 70% of the transplanted islet mass. Activation of the complement cascade and coagulation factors has been implicated in initiating the destruction of the islet graft. In this study, we analyzed the gene expression changes in islet cells following exposure to type 1 diabetes mellitus serum (T1DM). Isolated human pancreatic islet cells were cultured for two days to stabilize islet cell gene expression. Cultured islets were divided into three groups for treatment as follows: group 1 was treated with autologous donor serum, while groups two and three were treated with sera from ABO-matched allogeneic donors or autoantibody positive type 1 diabetic patient, respectively. Complement was detected using anti-C3 FITC and CH50 assay. Islet gene expression was analyzed using Illumina micro-array technology. Results were confirmed using real-time PCR. Immunofluorescent imaging demonstrated complement deposition only in the T1DM condition. Gene array and class prediction analysis generated a list of 50 genes that were able to predict the effect of T1DM serum on islets. Quantitative PCR corroborated microarray results. Both techniques demonstrated upregulation of MMP9 (243%), IL-1â (255%), IL-11 (220%), IL-12A (132%), RAD (343%) and a concomitant downregulation of IL-1RN (64%) in islets treated with T1DM serum. Islets treated with T1DM serum overexpressed genes associated with angiogenesis while decreasing transcription of genes that protect islets from inflammatory cytokines and reactive oxygen species.

Original languageEnglish
Pages (from-to)312-319
Number of pages8
JournalIslets
Volume4
Issue number4
Publication statusPublished - Jul 2012
Externally publishedYes

Fingerprint

Gene Expression
Type 1 Diabetes Mellitus
Serum
Islets of Langerhans
Genes
Complement Hemolytic Activity Assay
Tissue Donors
Interleukin-11
Islets of Langerhans Transplantation
Blood Coagulation Factors
Fluorescein-5-isothiocyanate
Complement Activation
Cell Transplantation
Interleukin-1
Autoantibodies
Real-Time Polymerase Chain Reaction
Reactive Oxygen Species
Up-Regulation
Down-Regulation
Cytokines

Keywords

  • Autoimmunity
  • Complement
  • Inflammation
  • Islet cell transplantation
  • Microarray

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Jackson, A. M., Kanak, M. A., Grishman, E. K., Chaussabel, D. J., Levy, M. F., & Naziruddin, B. (2012). Gene expression changes in human islets exposed to type 1 diabetic serum. Islets, 4(4), 312-319.

Gene expression changes in human islets exposed to type 1 diabetic serum. / Jackson, Andrew M.; Kanak, Mazhar A.; Grishman, Ellen K.; Chaussabel, Damien J.; Levy, Marlon F.; Naziruddin, Bashoo.

In: Islets, Vol. 4, No. 4, 07.2012, p. 312-319.

Research output: Contribution to journalArticle

Jackson, AM, Kanak, MA, Grishman, EK, Chaussabel, DJ, Levy, MF & Naziruddin, B 2012, 'Gene expression changes in human islets exposed to type 1 diabetic serum', Islets, vol. 4, no. 4, pp. 312-319.
Jackson AM, Kanak MA, Grishman EK, Chaussabel DJ, Levy MF, Naziruddin B. Gene expression changes in human islets exposed to type 1 diabetic serum. Islets. 2012 Jul;4(4):312-319.
Jackson, Andrew M. ; Kanak, Mazhar A. ; Grishman, Ellen K. ; Chaussabel, Damien J. ; Levy, Marlon F. ; Naziruddin, Bashoo. / Gene expression changes in human islets exposed to type 1 diabetic serum. In: Islets. 2012 ; Vol. 4, No. 4. pp. 312-319.
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