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Title

Increased interleukin (IL)-1beta messenger ribonucleic acid expression in beta -cells of individuals with type 2 diabetes and regulation of IL-1beta in human islets by glucose and autostimulation

Authors
Böni-Schnetzler, Marianne
Thorne, Jeffrey
Marselli, Lorella
Ehses, Jan A.
Kerr-Conte, Julie
Pattou, Francois
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Published in Journal of Clinical Endocrinology & Metabolism. 2008, vol. 93, no. 10, p. 4065-74
Abstract CONTEXT: Elevated glucose levels impair islet function and survival, and it has been proposed that intraislet expression of IL-1beta contributes to glucotoxicity. OBJECTIVE: The objective was to investigate IL-1beta mRNA expression in near-pure beta-cells of patients with type 2 diabetes (T2DM) and study the regulation of IL-1beta by glucose in isolated human islets. METHODS: Laser capture microdissection was performed to isolate beta-cells from pancreas sections of 10 type 2 diabetic donors and nine controls, and IL-1beta mRNA expression was analyzed using gene arrays and PCR. Cultured human islets and fluorescence-activated cell sorter-purified human beta-cells were used to study the regulation of IL-1beta expression by glucose and IL-1beta. RESULTS: Gene array analysis of RNA from beta-cells of individuals with T2DM revealed increased expression of IL-1beta mRNA. Real-time PCR confirmed increased IL-1beta expression in six of 10 T2DM samples, with minimal or no expression in nine control samples. In cultured human islets, IL-1beta mRNA and protein expression was induced by high glucose and IL-1beta autostimulation and decreased by the IL-1 receptor antagonist IL-1Ra. The glucose response was negatively correlated with basal IL-1beta expression levels. Autostimulation was transient and nuclear factor-kappaB dependent. Glucose-induced IL-1beta was biologically active and stimulated IL-8 release. Low picogram per milliliter concentrations of IL-1beta up-regulated inflammatory factors IL-8 and IL-6. CONCLUSION: Evidence that IL-1beta mRNA expression is up-regulated in beta-cells of patients with T2DM is presented, and glucose-promoted IL-1beta autostimulation may be a possible contributor.
Keywords Autocrine Communication/drug effects/genetics/physiologyCells, CulturedDiabetes Mellitus, Type 2/genetics/metabolismGene Expression ProfilingGlucose/pharmacologyHumansInsulin-Secreting Cells/metabolismInterleukin-1beta/genetics/metabolism/pharmacologyInterleukin-6/geneticsInterleukin-8/geneticsIslets of Langerhans/drug effects/metabolismNF-kappa B/physiologyOligonucleotide Array Sequence AnalysisRNA, Messenger/metabolismUp-Regulation/drug effects
Identifiers
PMID: 18664535
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Supplemental data - III (19 Kb) - public document Free access
Other version: http://jcem.endojournals.org/cgi/content/full/93/10/4065
Structures
Research groups Fonction de l'îlot de Langerhans (324)
La transplantation d'îlots de Langerhans (623)
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BÖNI-SCHNETZLER, Marianne et al. Increased interleukin (IL)-1beta messenger ribonucleic acid expression in beta -cells of individuals with type 2 diabetes and regulation of IL-1beta in human islets by glucose and autostimulation. In: Journal of Clinical Endocrinology & Metabolism, 2008, vol. 93, n° 10, p. 4065-74. https://archive-ouverte.unige.ch/unige:1826

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Deposited on : 2009-05-28

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