Islet inflammation impairs the pancreatic beta-cell in type 2 diabetes.
ABSTRACT Onset of Type 2 diabetes occurs when the pancreatic beta-cell fails to adapt to the increased insulin demand caused by insulin resistance. Morphological and therapeutic intervention studies have uncovered an inflammatory process in islets of patients with Type 2 diabetes characterized by the presence of cytokines, immune cells, beta-cell apoptosis, amyloid deposits, and fibrosis. This insulitis is due to a pathological activation of the innate immune system by metabolic stress and governed by IL-1 signaling. We propose that this insulitis contributes to the decrease in beta-cell mass and the impaired insulin secretion observed in patients with Type 2 diabetes.
- SourceAvailable from: Ashfaque A Memon[show abstract] [hide abstract]
ABSTRACT: To investigate the associations between cytokines and insulin sensitivity in Swedish residents born in Iraq and Swedish residents born in Sweden. Cross-sectional study. Iraqi and Swedish origin residents of Rosengård area of Malmö, aged 45-65 years, were randomly selected from the census register. 194 (Iraqi, n=107; Swedish, n=87) participants agreed to participate in the study. Nineteen participants dropped out (Iraqi, n=11; Swedish, n=8). Participants who had already been diagnosed with type 2 diabetes mellitus (T2DM), those who could not participate in an oral glucose tolerance test and those who had a cold/fever at the time of blood sampling were excluded. In total, serum samples from 135 individuals of Swedish (n=62) and Iraqi (n=73) origin were included. Serum concentrations of a panel of 10 cytokines, comprising interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12 (p70), IL-13, interferon-γ and tumour necrosis factor-α were analysed by Luminex multiplex assay. In the whole study population, levels of all tested cytokines were inversely associated with insulin sensitivity index (ISI), independent of age, sex, body mass index (BMI), sedentary lifestyle and family history of T2DM (p ≤ 0.05). Interestingly, stratification of the study population according to country of birth showed a significant inverse association between all tested cytokines and ISI in the Iraqi-born population (p ≤ 0.01). The association was independent of age, sex, BMI, sedentary lifestyle and family history of T2DM. In contrast, with the exception for IL-6 (p=0.05), no other tested cytokine was found to be significantly associated with ISI in the Swedish-born population (p≥0.05). Our results show an association between cytokines and ISI in the Iraqi-born population but not in the Swedish-born population.BMJ Open 11/2013; 3(11):e003473. · 1.58 Impact Factor
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ABSTRACT: Pathogen and nutrient response pathways are evolutionarily conserved and highly integrated to regulate metabolic and immune homeostasis. Excessive nutrients can be sensed by innate pattern recognition receptors as danger signals either directly or through production of endogenous ligands or modulation of intestinal microbiota. This triggers the activation of downstream inflammatory cascades involving nuclear factor κB and mitogen-activated protein kinase and ultimately induces the production of inflammatory cytokines and immune cell infiltration in various metabolic tissues. The chronic low-grade inflammation in the brain, islet, liver, muscle, and adipose tissue further promotes insulin resistance, energy imbalance, and impaired glucose/lipid metabolism, contributing to the metabolic complications of obesity, such as diabetes and atherosclerosis. In addition, innate pathogen receptors have now emerged as a critical link between the intestinal microbiota and host metabolism. In this review we summarize recent studies demonstrating the important roles of innate pathogen receptors, including Toll-like receptors, nucleotide oligomerization domain containing proteins, and inflammasomes in mediating the inflammatory response to metabolic stress in different tissues and highlight the interaction of innate pattern recognition receptors, gut microbiota, and nutrients during the development of obesity and related metabolic disorders.The Journal of allergy and clinical immunology 08/2013; 132(2):287-94. · 9.17 Impact Factor
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ABSTRACT: Cell failure is crucial for the onset and progression of human type 2 diabetes, and a few studies have suggested that inflammation may play a role. Immune cell infiltration has been reported in subpopulations of islets in some cases of human type 2 diabetes, and altered gene expression of a few cytokines and chemokines has been observed in isolated islets and laser captured β-cells from diabetic subjects. Recent observations on the links between inflammation, apoptosis and autophagy are putting the focus on the possibility that modulating the autophagic processes could protect the β-cells from cytotoxicity induced by inflammatory mediators.