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Inflammation and Activated Innate Immunity in the Pathogenesis of Type 2 Diabetes

  1. John C. Pickup, DPHIL, FRCPATH
  1. From the Metabolic Unit, Guy’s, King’s and St. Thomas’s School of Medicine, Guy’s Hospital, London, U.K.
  1. Address correspondence and reprint requests to John Pickup, Metabolic Unit, Thomas Guy House, GKT School of Medicine, Guy’s Hospital, London SE1 9RT, U.K. E-mail: john.pickup{at}kcl.ac.uk
Diabetes Care 2004 Mar; 27(3): 813-823. https://doi.org/10.2337/diacare.27.3.813
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    Figure 1—

    The components of the innate immune system. Sentinel cells such as the macrophage detect potential environmental threats from infection, chemicals, and foods by PRRs that activate signaling pathways and release proinflammatory cytokines (IL-6 and TNF-α). Known PRRs include TLR-4, which senses bacterial LPS and the receptor for AGEs. Cytokines stimulate acute-phase protein production from the liver and also act on the brain to release adrenocorticotrophic hormone (and thereby cortisol from the adrenal gland) and activate the sympathetic nervous system with the release of catecholamines. Psychological stress can cause an acute-phase response via innervation of cytokine-producing cells and via activation of the sympathetic nervous system and adrenergic receptors on macrophages. Central cytokine-induced “sickness behavior” includes lethargy, sleep changes, and depression. The innate immune system also controls the adaptive (acquired) immune system via costimulatory molecule expression that is necessary for antigen presentation. SAA, serum amyloid A.

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    Figure 2—

    Several factors such as altered nutrition, inactivity, age, fetal metabolic programming, and genetic propensity are known activators of the innate immune system. Cytokine production leads to insulin resistance (possibly impaired insulin secretion), type 2 diabetes, and other components of the metabolic syndrome, such as dyslipidemia. Activated innate immunity is a possible common antecedent of both type 2 diabetes and atherosclerosis.

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Diabetes Care: 27 (3)

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March 2004, 27(3)
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Inflammation and Activated Innate Immunity in the Pathogenesis of Type 2 Diabetes
John C. Pickup
Diabetes Care Mar 2004, 27 (3) 813-823; DOI: 10.2337/diacare.27.3.813

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Inflammation and Activated Innate Immunity in the Pathogenesis of Type 2 Diabetes
John C. Pickup
Diabetes Care Mar 2004, 27 (3) 813-823; DOI: 10.2337/diacare.27.3.813
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    • Abstract
    • METHODS
    • INNATE IMMUNITY, INFLAMMATION, AND THE ACUTE-PHASE AND STRESS RESPONSE: WHAT THEY ARE AND HOW THEY ARE RELATED
    • THE ORIGINS OF THE ACTIVATED INNATE IMMUNITY PARADIGM
    • POSSIBLE MECHANISMS OF ACTIVATED INNATE IMMUNITY IN TYPE 2 DIABETES: CYTOKINES, FETAL PROGRAMMING, GENETICS, NUTRITION, INACTIVITY, STRESS, AND AGE
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