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Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2008-0396 Copyright © 2008 by The Endocrine Society Increased Interleukin (IL)-1β Messenger Ribonucleic Acid Expression in β-Cells of Individuals with Type 2 Diabetes and Regulation of IL-1β in Human Islets by Glucose and AutostimulationMarianne Böni-Schnetzler, Jeffrey Thorne, Géraldine Parnaud, Lorella Marselli, Jan A. Ehses, Julie Kerr-Conte, Francois Pattou, Philippe A. Halban, Gordon C. Weir and Marc Y. DonathClinic of Endocrinology and Diabetes (M.B.-S., J.A.E., M.Y.D.), University Hospital of Zurich, 8091 Zurich, Switzerland; Section of Islet Transplantation and Cell Biology (J.T., L.M., G.C.W.), Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215; Department of Genetic Medicine and Development (G.P., P.A.H.), University of Geneva, 1211 Geneva 4, Switzerland; and Thérapie Cellulaire du Diabète (J.K.-C., F.P.), Institut National de la Santé et de la Recherche Médicale Unit M 859, Faculté de Médecine, 59045 Lille Cedex, France Address all correspondence and requests for reprints to: Marianne Böni-Schnetzler, Ph.D., Clinic of Endocrinology and Diabetes, Department of Medicine, University Hospital, CH-8091 Zurich, Switzerland. E-mail: marianne.boeni{at}usz.ch. Context: Elevated glucose levels impair islet function and survival, and it has been proposed that intraislet expression of IL-1β contributes to glucotoxicity. Objective: The objective was to investigate IL-1β mRNA expression in near-pure β-cells of patients with type 2 diabetes (T2DM) and study the regulation of IL-1β by glucose in isolated human islets. Methods: Laser capture microdissection was performed to isolate β-cells from pancreas sections of 10 type 2 diabetic donors and nine controls, and IL-1β mRNA expression was analyzed using gene arrays and PCR. Cultured human islets and fluorescence-activated cell sorter-purified human β-cells were used to study the regulation of IL-1β expression by glucose and IL-1β.
Results: Gene array analysis of RNA from β-cells of individuals with T2DM revealed increased expression of IL-1β mRNA. Real-time PCR confirmed increased IL-1β expression in six of 10 T2DM samples, with minimal or no expression in nine control samples. In cultured human islets, IL-1β mRNA and protein expression was induced by high glucose and IL-1β autostimulation and decreased by the IL-1 receptor antagonist IL-1Ra. The glucose response was negatively correlated with basal IL-1β expression levels. Autostimulation was transient and nuclear factor- Conclusion: Evidence that IL-1β mRNA expression is up-regulated in β-cells of patients with T2DM is presented, and glucose-promoted IL-1β autostimulation may be a possible contributor. This article has been cited by other articles:
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B dependent. Glucose-induced IL-1β was biologically active and stimulated IL-8 release. Low picogram per milliliter concentrations of IL-1β up-regulated inflammatory factors IL-8 and IL-6. 
