Inflammatory Process in Type 2 Diabetes

Alexandraki, Krystallenia Ι.; Piperi, Christina; Kalofoutis, Christos; Singh, Jaipaul; Alaveras, Antonis; Kalofoutis, Anastasios

doi:10.1196/annals.1372.039

Cited by 284 publications

(207 citation statements)

References 307 publications

(542 reference statements)

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“…Indeed sub-clinical chronic inflammation is considered to be a constant partner of the hyperglycemic milieu and is also found in other pathological conditions including obesity, hypertension and atherosclerosis (Alexandraki et al, 2006). Evidence of inflammation is also found in clinical specimens from patients with diabetic retinopathy (Esser et al, 1995;Lutty et al, 1997;Meleth et al, 2005;Mitamura et al, 2001).…”

Section: Vascular Inflammation and Diabetic Retinopathymentioning

confidence: 99%

Vascular endothelial growth factor in eye disease

Penn

Madan

Caldwell

et al. 2008

Progress in Retinal and Eye Research

636

527

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Collectively, angiogenic ocular conditions represent the leading cause of irreversible vision loss in developed countries. In the U.S., for example, retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration are the principal causes of blindness in the infant, working age and elderly populations, respectively. Evidence suggests that vascular endothelial growth factor (VEGF), a 40 kDa dimeric glycoprotein, promotes angiogenesis in each of these conditions, making it a highly significant therapeutic target. However, VEGF is pleiotropic, affecting a broad spectrum of endothelial, neuronal and glial behaviors, and confounding the validity of anti-VEGF strategies, particularly under chronic disease conditions. In fact, among other functions VEGF can influence cell proliferation, cell migration, proteolysis, cell survival and vessel permeability in a wide variety of biological contexts. This article will describe the roles played by VEGF in the pathogenesis of retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration. The potential disadvantages of inhibiting VEGF will be discussed, as will the rationales for targeting other VEGF-related modulators of angiogenesis.

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Section: Vascular Inflammation and Diabetic Retinopathymentioning

confidence: 99%

Vascular endothelial growth factor in eye disease

Penn

Madan

Caldwell

et al. 2008

Progress in Retinal and Eye Research

636

527

View full text Add to dashboard Cite

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“…Low-grade chronic systemic inflammation has been associated with the process of aging and the pathogenesis or course of many age-related diseases (Alexandraki et al 2006;Vasan et al 2003;Joppa et al 2006;Beenakker et al 2010). Therefore, this chronic subclinical inflammatory state may be detrimental in older adults by contributing to the pathophysiology of or reflect chronic conditions that result in functional loss and disability or even directly impact muscle mass (e.g., cfr sarcopenia) (Roubenoff and Hughes 2000;Schaap et al 2009).…”

Section: Introductionmentioning

confidence: 99%

Interleukin-6 predicts short-term global functional decline in the oldest old: results from the BELFRAIL study

Adriaensen

Matheï

Vaes

et al. 2014

AGE

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The chronic inflammatory state at old age may contribute to the pathophysiology of or reflect chronic conditions resulting in loss of physical and mental functioning. Therefore, our objective was to examine the predictive value of a large battery of serum inflammatory markers as risk indicators for global functional decline and its specific physical and mental determinants in the oldest old. Global functional decline and specific aspects of physical and mental functional decline were assessed during an average of 1.66 years (±0.21) in a sample of 303 persons aged 80 years or older of the BELFRAIL study. Serum levels of 14 inflammatory proteins, including cytokines, growth factors, and acute phase proteins, were measured at baseline. Almost 20 % of the participants had a significant global functional decline over time. Interleukin (IL)-6 serum levels were uniquely positively associated with global functional decline, even after correcting for multiple confounders (odds ratio 1.51). Odds ratios for the individual aspects (physical dependency, physical performance, cognition, and depression) of functioning were lower, and composite scores of physical or mental decline were not significant. The proportion of global functional decline exhibited a dose-response curve with increasing levels of IL-6. Thus, IL-6 is an independent risk indicator for accelerated global functional decline in the oldest old. Our results suggest that simple serum levels of IL-6 may be very useful in short-term identification or evaluation of global functional status in the oldest old.

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“…␣4(Y991A) monocyte/macrophages exhibit reduced chemotaxis toward MCP-1. MCP-1 is an important monocyte chemoattractant and is particularly implicated in the mobilization of monocytes from the bone marrow and the infiltration of adipose tissue with monocyte/ macrophages (34,35). Thus, we hypothesized that the decreased 7/4…”

Section: Preventing Obesity-induced Insulin Resistancementioning

confidence: 99%

Blockade of α4 Integrin Signaling Ameliorates the Metabolic Consequences of High-Fat Diet–Induced Obesity

et al. 2008

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OBJECTIVE-Many prevalent diseases of advanced societies, such as obesity-induced type 2 diabetes, are linked to indolent mononuclear cell-dependent inflammation. We previously proposed that blockade of ␣4 integrin signaling can inhibit inflammation while limiting mechanism-based toxicities of loss of ␣4 function. Thus, we hypothesized that mice bearing an ␣4(Y991A) mutation, which blocks signaling, would be protected from development of high-fat diet-induced insulin resistance.RESEARCH DESIGN AND METHODS-Six-to eight-weekold wild-type and ␣4(Y991A) C57Bl/6 male mice were placed on either a high-fat diet that derived 60% calories from lipids or a chow diet. Metabolic testing was performed after 16 -22 weeks of diet.RESULTS-␣4(Y991A) mice were protected from development of high-fat diet-induced insulin resistance. This protection was conferred on wild-type mice by ␣4(Y991A) bone marrow transplantation. In the reverse experiment, wild-type bone marrow renders high-fat diet-fed ␣4(Y991A) acceptor animals insulin resistant. Furthermore, fat-fed ␣4(Y991A) mice showed a dramatic reduction of monocyte/macrophages in adipose tissue. This reduction was due to reduced monocyte/macrophage migration rather than reduced monocyte chemoattractant protein-1 production. CONCLUSIONS-␣4integrins contribute to the development of HFD-induced insulin resistance by mediating the trafficking of monocytes into adipose tissue; hence, blockade of ␣4 integrin signaling can prevent the development of obesity-induced insulin resistance.

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Inflammatory Process in Type 2 Diabetes

Cited by 284 publications

References 307 publications

Vascular endothelial growth factor in eye disease

Vascular endothelial growth factor in eye disease

Interleukin-6 predicts short-term global functional decline in the oldest old: results from the BELFRAIL study

Blockade of α4 Integrin Signaling Ameliorates the Metabolic Consequences of High-Fat Diet–Induced Obesity

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