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      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.

      The Journal of Clinical Endocrinology and Metabolism

      drug effects, Autocrine Communication, genetics, physiology, Cells, Cultured, Diabetes Mellitus, Type 2, metabolism, Gene Expression Profiling, Glucose, pharmacology, Humans, Insulin-Secreting Cells, Interleukin-1beta, Interleukin-6, Interleukin-8, Islets of Langerhans, NF-kappa B, Oligonucleotide Array Sequence Analysis, RNA, Messenger, Up-Regulation

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          Abstract

          Elevated glucose levels impair islet function and survival, and it has been proposed that intraislet expression of IL-1beta contributes to glucotoxicity. 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. 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. 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. 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.

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          Author and article information

          Journal
          10.1210/jc.2008-0396
          2579638
          18664535

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