EXPRESSION OF SOCS PROTEINS PROTECTS PANCREATIC BETA CELLS FROM GLUCOSE AND INTERLEUKIN-1β-INDUCED APOPTOSIS.

Abstract

Type 2 diabetes is characterized by beta-cell apoptosis and impaired insulin secretion. Chronic exposure of islets to high glucose accelerates this process, so-called glucotoxicity. This involves proinflammatory cytokines, specifically interleukin-1β. SOCS (suppressors of cytokine signaling) genes control cytokine action. We hypothesize that SOCS genes protect beta cells from apoptosis. Human islets were transfected with GFP, cis, SOCS-1, SOCS-2, and SOCS-3 adenoviruses. After culture at 5.5 mM (control), 11.1 or 33.3 mM glucose with or without IL-1β, apoptosis was measured by the TUNEL assay, SOCS-3 expression by Western blot analysis, and gene expression by quantitative RT-PCR. Western blot analysis revealed a 20-fold induction of SOCS-3 expression by 2 ng/mL IL-1β and 15-fold by 33.3 mM glucose. In parallel, exposure of islets to 2 ng/mL IL-1β or 33.3 mM glucose induced a 3.3-fold or 2.95-fold increase in beta-cell apoptosis, respectively (p