Metabolic Activity of Diabetic Monocytes

Kitahara, Mitsuo; Eyre, Harmon J.; Lynch, Robert E.; Rallison, Marvin L.; Hill, Harry R.

doi:10.2337/diab.29.4.251

Cited by 74 publications

(21 citation statements)

References 14 publications

(14 reference statements)

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“…Data of O 2 -generation of diabetic cells demonstrated that regardless of the type of diabetes, diabetics produced significantly more O 2 -upon PMA and OPZ stimulation and under the resting state compared with normal mononuclear phagocytes. This finding confirms two previous studies by Kitahara et al [3] and Devaraj and Jialal [28] and could be associated with atherogenicity of diabetic macrophages [29,30], exaggerated tissue damage [31,32], nephropathy [33], and impaired wound healing [34]. The hyper-responsive phenotype of diabetic mononuclear phagocytes suggests that the cells are somehow primed under diabetic conditions.…”

Section: Discussionsupporting

confidence: 80%

“…There are some controversial findings regarding O 2 generation by diabetic monocytes. Some studies [2][3][4] reported that O 2 -generation was elevated in diabetes, and another study found that it was decreased in Type 2 diabetes mellitus (DM) [5]. In this study, the oxidative burst from diabetic monocytes was evaluated thoroughly, and the effects of hyperglycemia were investigated.…”

Section: Introductionmentioning

confidence: 99%

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Activation of RAGE induces elevated O2− generation by mononuclear phagocytes in diabetes

Ding

Kantarcı

Hastürk

et al. 2006

Journal of Leukocyte Biology

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Oxidative stress has been found to play a role in the pathogenesis of diabetic complications. The aim of this study was to define the oxidative burst of diabetic monocytes to characterize the phenotype associated with poor diabetic control. Superoxide (O 2 -) is the first molecule generated during the respiratory burst of phagocytes by NADPH oxidase, and its generation by monocytes from 26 controls and 34 diabetic subjects was evaluated in this study. Under resting states or stimulation by PMA or opsonized zymosan, diabetic monocytes produce significantly more O 2 -than nondiabetic cells. The increased O 2 -generation was found to be correlated with glycemic control (glycated hemoglobin) of patients. To clarify the effects of hyperglycemia on O 2 -generation, normal human monocytes were treated with receptor for advanced glycation endproducts (RAGE) ligands (AGE protein and S100B) or high glucose media before stimulation. RAGE ligands and high glucose concentration increased O 2 -generation from human mononuclear phagocytes. RAGE ligands, specifically and potently, increased O 2 -generation from mononuclear phagocytes, and high-glucose effects were associated with correspondingly increased osmotic pressure. Differentiated THP-1 cells, from a human monocytic cell line, were used as a model of human monocytes to study the effects of S100B, the RAGE ligand. It was confirmed that RAGE is involved in the priming of O 2 -generation by S100B. This study demonstrates that RAGE ligands can contribute significantly to the hyperresponsive phenotype of diabetic monocytes, which might be reversible by blocking the RAGE or controlling the presence of RAGE ligands by controlling hyperglycemia.

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Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Activation of RAGE induces elevated O2− generation by mononuclear phagocytes in diabetes

Ding

Kantarcı

Hastürk

et al. 2006

Journal of Leukocyte Biology

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“…onsiderable evidence has been accumulated to suggest that the production of reactive oxygen species (ROS) is increased in diabetic patients, especially in those with poor glycemic control (1)(2)(3). Excessive ROS can accelerate oxidative damage to macromolecules, including lipids and proteins, as well as to DNA.…”

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confidence: 99%

Serum 8-Hydroxy-Guanine Levels Are Increased in Diabetic Patients

et al. 2001

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OBJECTIVE -The production of reactive oxygen species is increased in diabetic patients, especially in those with poor glycemic control. We have investigated oxidative damage in type 2 diabetic patients using serum 8-hydroxyguanine (8-OHG) as a biomarker.RESEARCH DESIGN AND METHODS -We studied 41 type 2 diabetic patients and compared them with 33 nondiabetic control subjects. Serum 8-OHG concentration was assayed using high-pressure liquid chromatography.RESULTS -The type 2 diabetic patients had significantly higher concentrations of 8-OHG in their serum than the control subjects (5.03 Ϯ 0.69 vs. 0.96 Ϯ 0.15 pmol/ml; P Ͻ 0.01). There was no association between the levels of 8-OHG and HbA 1c . We also could not find any correlation between serum 8-OHG levels and age, duration of diabetes, serum lipids, or creatinine or albumin excretion rate. Creatinine clearance showed marginal correlation with serum 8-OHG levels (P ϭ 0.06). Among the diabetic patients, those with proliferative retinopathy had significantly higher 8-OHG levels than those with nonproliferative retinopathy or without retinopathy. Likewise, the serum 8-OHG levels in patients who had advanced nephropathy (azotemia) were higher than in patients with normoalbuminuria, microalbuminuria, or overt proteinuria.CONCLUSIONS -Our findings show that measuring serum 8-OHG is a novel convenient method for evaluating oxidative DNA damage. Diabetic patients, especially those with advanced microvascular complications, had significantly higher serum 8-OHG levels; this suggests that such changes may contribute to the development of microvascular complications of diabetes. Diabetes Care 24:733-737, 2001C onsiderable evidence has been accumulated to suggest that the production of reactive oxygen species (ROS) is increased in diabetic patients, especially in those with poor glycemic control (1-3). Excessive ROS can accelerate oxidative damage to macromolecules, including lipids and proteins, as well as to DNA. An increased production of malondialdehyde (MDA), a marker of lipid peroxidation, has been demonstrated in the erythrocyte membranes of diabetic patients, along with a depressed erythrocyte content of reduced glutathione (4). Moreover, there is a significant relationship between markers of lipid peroxidation and metabolic control in both type 1 and type 2 diabetic patients (5). Although there are fewer data regarding the oxidation of protein, a recent study by Suzuki et al. (6) demonstrated local oxidative stress and carbonyl modification of proteins in diabetic glomerulopathy.8-Hydroxydeoxyguanosine (8-OHdG), an ROS-induced modification of a purine residue in DNA, is a sensitive index of oxidative DNA damage (7). 8-OHdG in plasma increases with age (8), with cigarette smoking (9), and during tumorigenesis (10). The urinary level of this molecule is now considered a biomarker of the total systemic oxidative stress in vivo. Dandona et al. (11) demonstrated that type 1 and type 2 diabetic patients had a significantly higher concentration of 8-OH-dG in their monon...

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“…These included: normal antigen presentation activity [33], reduced numbers of circulating monocytes and reduced phagocytosis [34], normal cell migration distance, but fewer migrating cells [35] and reduced number of phagocytic cells [36]. One study has reported increased chemiluminescence activity, but this was attributed to the increased levels of blood glucose [37].…”

Section: Discussionmentioning

confidence: 99%

Circulating monocytes are activated in newly diagnosed type 1 diabetes mellitus patients

Josefsen¹,

Nielsen

Lorentzen

et al. 1994

Clinical and Experimental Immunology

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SLVIMARYInvestigations in the BB rat and the non-obese diabetic (NOD) mouse have provided substantial evidence for the involvement of the monocyte/macrophage system in the development of type 1 diabetes mellitus. However, it is not known whether monocytes play the same role in the pathogenesis of human type 1 diabetes. We investigated this problem iti a longitudinal study of 29 recent-onset type 1 diabetes mellitus patients. Monocyte chemotaxis, phagocytosis and superoxide production as well as metabolic and haematoJogical parameters were studied immediately after diagnosis and 6 months later. At diagnosis the patients had activated casein and C5a chemotaxis (casein 70 ± 9 versus 150 ± 5 (mean ± s.e.m.), P < 0 001; C5a 137 ± 10 versus 158 ±5, Z'< 0 05 (activation immobilizes monocytes, reducing the measured values)), and activated superoxide production (3-6 ± 0 3 versus 3-0 ± 0 3, P < 0-05), After 6 months casein chemotaxis (115 ±16 versus 150 ±5, P < 0 05) and Candida phagocytosis (3 3 ±01 versus 2-8 ±0-2. P<000])were still activated. There was no correlation with other clinical or paraclinical parameters. We conclude that the circulating monocytes in newly diagnosed type 1 diabetes patients are activated. U is reasonable to expect that monocytes at the local site of inflammation in pancreas are even further activated. This could play a pathogenic role in ii cell destruction.Keywords monocytes macrophages superoxide production phagocytosis chemotaxis type 1 diabetes mellitus newly diagnosed INTRODUCTIO.N

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Metabolic Activity of Diabetic Monocytes

Cited by 74 publications

References 14 publications

Activation of RAGE induces elevated O2− generation by mononuclear phagocytes in diabetes

Activation of RAGE induces elevated O2− generation by mononuclear phagocytes in diabetes

Serum 8-Hydroxy-Guanine Levels Are Increased in Diabetic Patients

Circulating monocytes are activated in newly diagnosed type 1 diabetes mellitus patients

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