Considerations for Defining Cytokine Dose, Duration, and Milieu That Are Appropriate for Modeling Chronic Low-Grade Inflammation in Type 2 Diabetes

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hyperglycemia 3 endocrinologydiseases
obesity 11 endocrinologydiseases

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hyperglycemia 9274 [[47]]. We reported that serum levels of IL-1beta and IL-6 in diabetes-prone mice at an age before hyperglycemia developed were 2-3 times higher than for age-matched heterozygous control mice, suggesting that low-grade
hyperglycemia 20757 Although the inflammatory environment is dynamic, we focused on cytokines involved prior to the onset of hyperglycemia (the prediabetic stage). Several observations served as our rationale for developing this model of circulating
hyperglycemia 21114 in humans [[47]]. Second, increased levels of IL-1beta and IL-6 were observed in db/db mice prior to hyperglycemia or substantial differences in weight (<10%) compared to control mice [[74]]. Differences in several
obesity 1388 macrophages/immune cells, and (3) from increased circulating levels of proinflammatory cytokines due to obesity , presumably coming from inflamed adipose tissue. These differences between T1D and T2D are reflected
obesity 5472 consistent cytotoxic effects on human islets [[3], [4], [34], [37], [38]]. In T2D, the metabolic stress of obesity is thought to elevate cytokine production in adipose tissue [[39]–[43]] and other organs to a lesser
obesity 7595 questions must be addressed:What cytokines and chemokines are elevated in the systemic circulation in obesity and T2D that can negatively impact islet function?What immune cells are found in or near islets that
obesity 9527 early in the disease process [[74]].In addition, many other cytokines and chemokines are increased in obesity including leptin, resistin, IL-7, IL-8, retinol binding protein- (RBP-) 4, plasminogen activator inhibitor-
obesity 9787 (CXCL5), visfatin, chemerin, and vaspin [[75], [76]]. Other cytokines are decreased with increased obesity including adiponectin, IL-10, and omentin [[75], [76]]. We conducted a 32-plex cytokine detection array
obesity 10293 were highly variable. However, CXCL1 and CXCL5 were increased significantly in serum at the onset of obesity and T2D. We further showed that exposure to circulating concentrations of these chemokines synergistically
obesity 10999 as IL-1beta and IL-6 on the development of T2D in humans [[47]]. IFN-gamma appears to be elevated in obesity and may play a role in islet dysfunction in T2D [[78], [79]]. However, at present there is not sufficient
obesity 11324 localized within islets in models of T2D. Additional studies are needed to determine the full milieu of obesity -associated cytokines and the extent to which this milieu of circulating cytokines can impact islet function.3.2.
obesity 17682 increases in circulating cytokines, thus reproducing cytokine levels observed in low-grade inflammation in obesity . The increased circulating levels of IL-1beta + IL-6 were insufficient to impact physiology in these
obesity 22721 elevating specific circulating cytokines related to chronic low-grade inflammation in T2D, independent of obesity .6. Final ThoughtsDifferences in susceptibility to cytokine-induced damage between diabetes-prone and
obesity 23141 diseases could play out in this way? The relatively small increases in circulating cytokines caused by obesity or other chronic inflammatory conditions could conceivably contribute to a plethora of conditions including

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