Abstract
The escalating epidemic of obesity has driven the prevalence of both type 1 and 2 diabetes mellitus to historically high levels. Chronic low-grade inflammation, which is present in both type 1 and type 2 diabetics, contributes to the pathogenesis of insulin resistance. The accumulation of activated innate immune cells in metabolic tissues results in release of inflammatory mediators, in particular, IL-1β and TNFα, which promote systemic insulin resistance and β-cell damage. In this article, we discuss the central role of innate immunity and, in particular, the macrophage in insulin sensitivity and resistance, β-cell damage, and autoimmune insulitis. We conclude with a discussion of the therapeutic implications of this integrated understanding of diabetic pathology.
Publication types
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Research Support, N.I.H., Extramural
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Review
MeSH terms
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Adaptive Immunity / physiology
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Adipose Tissue / immunology
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Adipose Tissue / physiopathology
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B-Lymphocytes / immunology
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Cytokines / metabolism
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Diabetes Mellitus, Type 1 / immunology*
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Diabetes Mellitus, Type 2 / immunology*
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Humans
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Immunity, Innate*
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Inflammasomes / physiology
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Inflammation / physiopathology
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Inflammation Mediators / immunology
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Inflammation Mediators / physiology*
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Insulin Resistance / immunology
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Insulin Resistance / physiology*
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Interleukin-1beta / immunology
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Kupffer Cells / physiology
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Liver / physiopathology
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Macrophages / immunology
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Macrophages / physiology*
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Obesity / immunology
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Obesity / physiopathology
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Receptor, Insulin / physiology
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Tumor Necrosis Factor-alpha / immunology
Substances
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Cytokines
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Inflammasomes
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Inflammation Mediators
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Interleukin-1beta
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Tumor Necrosis Factor-alpha
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Receptor, Insulin