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Horm Metab Res 2003; 35(7): 407-414
DOI: 10.1055/s-2003-41621
Original Basic
© Georg Thieme Verlag Stuttgart · New York

IGFs, Basic FGF, and Glucose Modulate Proliferation and Apoptosis Induced by IFNγ but not by IL-1β in Rat INS-1E β-cells

K.  Raile 1 , A.  Berthold 1 , U.  Banning 1 , F.  Horn 2 , G.  Pfeiffer 2 , W.  Kiess 1
  • 1Research Laboratory, Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany
  • 2Dept. of Immunology, Faculty of Medicine, University of Leipzig, Leipzig, Germany
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Publication History

Received 16 January 2003

Accepted after Revision 26 March 2003

Publication Date:
21 August 2003 (online)

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Abstract

We investigated the effects of glucose and β-cell growth factors (IGF-I, IGF-II, bFGF) on growth and apoptosis in the presence and absence of apoptosis inducing cytokines (IFNγ, Il-1β, TNFα). Rat INS-1E β-cell viability was measured by WST-1 viability assay and cell counting, apoptosis by FACS analysis of annexin-V-FITC and fluorescein-dUTP (TUNEL-staining)-positive cells. Glucose alone maintained INS-1E β-cell viability at high physiological concentrations (6.2 - 12.5 mmol/l), addition of IGF-II alone or in combination with bFGF further increased these glucose effects. The cytokines IFNg and IL-1β, but not TNFα strongly induced INS-1E β-cell apoptosis. Interestingly, glucose alone induced apoptosis at extremely low or very high concentrations. In combination with IFNg, low glucose (1.6 mmol/l) increased apoptosis by 25.6 % (1SD 5.0 %) and high glucose (50 mmol/l) by 22.8 % (1SD 2.8 %) compared to 12.5 mmol/l glucose. In contrast, glucose failed to modulate IL-1β-induced apoptosis. Most importantly, IGF-II and bFGF inhibited apoptosis induced by IFNg, but not by IL-1β. Therefore, IGF signaling, supported by bFGF and optimal glucose levels, maintains β-cell viability in vitro. Cytokines IFNg and IL-1β differentially interfere with intracellular signaling cascades stimulated by IGFs and bFGF or glucose, respectively.

Key words

Glucose - Growth factors - Cytokines - β-cells - Apoptosis

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