Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-7322
Böni-Schnetzler, M; Thorne, J; Parnaud, G; Marselli, L; Ehses, J A; Kerr-Conte, J; Pattou, F; Halban, P A; Weir, G C; Donath, M Y (2008). 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. Journal of Clinical Endocrinology and Metabolism, 93(10):4065-4074.
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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.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Clinic for Endocrinology and Diabetology|
04 Faculty of Medicine > Center for Integrative Human Physiology
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Deposited On:||16 Dec 2008 11:37|
|Last Modified:||28 Nov 2013 00:53|
|Citations:||Web of Science®. Times Cited: 91|
Scopus®. Citation Count: 95
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