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Related Experiment Videos

IL-1 produced and released endogenously within human islets inhibits beta cell function

M Arnush1, M R Heitmeier, A L Scarim

  • 1Edward A. Doisy Department of Biochemistry and Molecular Biology, St. Louis University School of Medicine, St. Louis, Missouri 63104, USA.

The Journal of Clinical Investigation
|August 6, 1998
PubMed
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Resident macrophages release interleukin-1 (IL-1), which activates nitric oxide synthase (iNOS) in human islets. This process, crucial in autoimmune diabetes, impairs beta cell function and insulin secretion.

Area of Science:

  • Immunology
  • Endocrinology
  • Diabetes Research

Background:

  • Resident macrophages in pancreatic islets are implicated in autoimmune diabetes pathogenesis.
  • Interleukin-1 (IL-1) is a key inflammatory cytokine involved in immune responses.

Purpose of the Study:

  • To investigate if endogenous IL-1 production by islet macrophages inhibits beta cell function.
  • To elucidate the role of IL-1 and nitric oxide in cytokine-induced beta cell dysfunction.

Main Methods:

  • Human islets were treated with tumor necrosis factor (TNF), lipopolysaccharide (LPS), and interferon-gamma (IFN-gamma).
  • Inducible nitric oxide synthase (iNOS) expression, nitric oxide production, and insulin secretion were measured.
  • IL-1 receptor antagonist protein (IRAP) and aminoguanidine were used to block IL-1 and iNOS pathways.

Related Experiment Videos

  • Reverse transcriptase polymerase chain reaction and immunohistochemistry were employed to identify IL-1 sources.

    • Main Results:

    • TNF + LPS + IFN-gamma treatment induced iNOS expression, nitric oxide production, and inhibited insulin secretion.
    • IL-1 receptor blockade and iNOS inhibition attenuated these inhibitory effects.
    • Human islets expressed IL-1alpha and IL-1beta mRNA upon cytokine stimulation.
    • Resident macrophages were identified as the source of IL-1 in human islets.

    Conclusions:

    • Cytokine-induced beta cell dysfunction in human islets is mediated by IL-1-dependent nitric oxide production.
    • Activated islet macrophages release IL-1, contributing to beta cell damage in autoimmune diabetes.
    • Cellular damage can stimulate IL-1 release from islet macrophages.