Hyperglycemia Induces Monocytic Release of Interleukin-6 via Induction of Protein Kinase C-α and -β

Devaraj, Sridevi; Venugopal, Senthil K.; Singh, U. S.; Jialal, Ishwarlal

doi:10.2337/diabetes.54.1.85

Cited by 190 publications

(145 citation statements)

References 33 publications

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“…In a laboratory study, monocytic cells were cultured in the presence of 5.5 mmol/l (normal) or 15 mmol/l (high) glucose and mannitol. Secreted IL-6, intracellular IL-6, and IL-6 mRNA were found to be significantly increased with hyperglycemia (P < 0.001) [48]. In addition, Qi and colleagues found that diets high in fiber may increase plasma adiponectin concentrations in diabetic patients [49] and adiponectin has been found to have profound anti-inflammatory effects [50].…”

Section: Discussionmentioning

confidence: 99%

Association between dietary fiber and markers of systemic inflammation in the Women's Health Initiative Observational Study

et al. 2008

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Objective-Systemic inflammation may play an important role in the development of atherosclerosis, type 2 diabetes, and some cancers. Few studies have comprehensively assessed the direct relationships between dietary fiber and inflammatory cytokines, especially in minority populations. Using baseline data from 1,958 postmenopausal women enrolled in the Women's Heath Initiative Observational Study, we examined cross-sectional associations between dietary fiber intake and markers of systemic inflammation (including serum C-reactive protein (hs-CRP), interleukin 6 (IL-6), and tumor necrosis factor α receptor 2 (TNF-α-R2)), as well as differences in these associations by ethnicity.Method-Multiple linear regression models were used to assess the relationship between fiber intake and makers of systemic inflammation.Results-After adjustment for covariates, intake of dietary fiber were inversely associated with both IL-6 (P values for trend were 0.01 for total fiber, 0.004 for soluble fiber, and 0.001 for insoluble fiber) and TNF-α-R2 (P values for trend were 0.002 for total, 0.02 for soluble, and <0.001 for insoluble fiber). Although the sample sizes were small in minority Americans, results were generally Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conclusions-These findings lend support to the hypothesis that a high-fiber diet is associated with lower plasma levels of IL-6 and TNF-α-R2. Contrary to previous reports, however, there was no association between fiber and hs-CRP among postmenopausal women. Future studies on the influence of diet on inflammation should include IL-6 and TNF-α-R2 and enroll participants from ethnic minorities. NIH Public Access

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Section: Discussionmentioning

confidence: 99%

Association between dietary fiber and markers of systemic inflammation in the Women's Health Initiative Observational Study

et al. 2008

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“…DAG have been implicated in the development of IR via activation of specific protein kinase C (PKC) isoforms [5]. PKC is known to induce IL-6 synthesis [14]. However, ceramides seemed to be more strongly associated with IL-6 levels than DAG, independently of the degree of IR as assessed by HOMA-IR index.…”

Section: Discussionmentioning

confidence: 99%

Link between plasma ceramides, inflammation and insulin resistance: association with serum IL-6 concentration in patients with coronary heart disease

et al. 2009

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Aims/hypothesis Ceramides and IL-6 have a role in immune-inflammatory responses and cardiovascular diseases, and are suggested to be involved in insulin and glucose metabolism. We sought to assess the associations of circulating levels of IL-6, TNF-α and high-sensitivity C reactive protein (hsCRP), which are inflammatory markers related to insulin resistance (IR), with the plasma lipid metabolites ceramides and diacylglycerols (DAG) in patients with CHD. Methods Cross-sectional analyses were carried out on data from 33 patients with CHD. Serum levels of the inflammatory markers and plasma lipid metabolites (lipidomics approach performed by ultra-performance liquid chromatography coupled to electrospray ionisation MS) were measured at the same time point as insulin resistance (IR) (HOMA-IR index).Results Serum circulating levels of IL-6 were strongly correlated with plasma ceramide concentrations (r=0.59, p<0.001). Adjustments for serum TNF-α or hsCRP levels, smoking, BMI, age, sex or HOMA-IR did not change the results (p<0.001). After adjustments for the effect of serum inflammatory markers (TNF-α or hsCRP), HOMA-IR and BMI the correlation between plasma DAG and serum IL-6 (r=0.33) was also significant (p<0.03). In a linear regression model, circulating levels of both ceramides and TNF-α had a significant independent influence on circulating levels of IL-6, altogether accounting for 41% of its variation (p<0.001). Conclusions/interpretation Our results strongly suggest that the link between ceramides, IR and inflammation is related to the inflammatory marker IL-6. Ceramides may contribute to the induction of inflammation involved in IR states that frequently coexist with CHD.

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“…However, other studies suggest that glucose-induced superoxide formation stems from glucose-6-phosphate dehydrogenase and phosphokinase C-dependent activation of NAD(P)H oxidase [7]. Subsequently, the production of pro-inflammatory immune mediators occurs via the activation of mitogen-activated kinases p38 and Jun N-terminal kinase (JNK), other tyrosine kinases, transcription factors such as transcription factor activator protein-1 (AP-1) and nuclear factor κB (NFκB), and/or poly(ADPribose) polymerase [8,9].…”

Section: Introductionmentioning

confidence: 99%

The global diabetes epidemic as a consequence of lifestyle-induced low-grade inflammation

Kolb¹,

2009

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The recent major increase in the global incidence of type 2 diabetes suggests that most cases of this disease are caused by changes in environment and lifestyle. All major risk factors for type 2 diabetes (overnutrition, low dietary fibre, sedentary lifestyle, sleep deprivation and depression) have been found to induce local or systemic low-grade inflammation that is usually transient or milder in individuals not at risk for type 2 diabetes. By contrast, inflammatory responses to lifestyle factors are more pronounced and prolonged in individuals at risk of type 2 diabetes and appear to occur also in the pancreatic islets. Chronic low-grade inflammation will eventually lead to overt diabetes if counter-regulatory circuits to inflammation and metabolic stress are compromised because of a genetic and/or epigenetic predisposition. Hence, it is not the lifestyle change per se but a deficient counter-regulatory response in predisposed individuals which is crucial to disease pathogenesis. Novel approaches of intervention may target these deficient defence mechanisms.

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Hyperglycemia Induces Monocytic Release of Interleukin-6 via Induction of Protein Kinase C-α and -β

Cited by 190 publications

References 33 publications

Association between dietary fiber and markers of systemic inflammation in the Women's Health Initiative Observational Study

Association between dietary fiber and markers of systemic inflammation in the Women's Health Initiative Observational Study

Link between plasma ceramides, inflammation and insulin resistance: association with serum IL-6 concentration in patients with coronary heart disease

The global diabetes epidemic as a consequence of lifestyle-induced low-grade inflammation

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