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Scientific article
English

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

Published inThe Journal of clinical endocrinology and metabolism, vol. 93, no. 10, p. 4065-4074
Publication date2008
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/physiology
  • Cells, Cultured
  • Diabetes Mellitus, Type 2/genetics/metabolism
  • Gene Expression Profiling
  • Glucose/pharmacology
  • Humans
  • Insulin-Secreting Cells/metabolism
  • Interleukin-1beta/genetics/metabolism/pharmacology
  • Interleukin-6/genetics
  • Interleukin-8/genetics
  • Islets of Langerhans/drug effects/metabolism
  • NF-kappa B/physiology
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger/metabolism
  • Up-Regulation/drug effects
Citation (ISO format)
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: The Journal of clinical endocrinology and metabolism, 2008, vol. 93, n° 10, p. 4065–4074. doi: 10.1210/jc.2008-0396
Main files (1)
Article (Accepted version)
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Secondary files (3)
Identifiers
ISSN of the journal0021-972X
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