Inflammatory Cytokines and the Risk of Cardiovascular Complications in Type 2 Diabetes

Mahmoud, Fadia; Al-Ozairi, Ebaa

doi:10.1155/2013/931915

Cited by 54 publications

(36 citation statements)

References 22 publications

(31 reference statements)

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“…It is well recognised that NF-κB transcriptional activity directly controls the main cytokine drivers of the Th1 response [7,47]. Furthermore, elevated levels of Th1 cytokines correlate with proteinuria [48] and the risk of cardiovascular complications [49] in patients with type 2 diabetes. Consistent with this, our findings indicate that regulation of the systemic Th1-mediated immunoinflammatory response may account, at least in part, for the in vivo protective effect of NBD in diabetic mice.…”

Section: Resultsmentioning

confidence: 99%

Peptide-based inhibition of IκB kinase/nuclear factor-κB pathway protects against diabetes-associated nephropathy and atherosclerosis in a mouse model of type 1 diabetes

et al. 2015

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Aims/hypothesis The canonical nuclear factor-κB (NF-κB) pathway mediated by the inhibitor of NF-κB kinase (IKK) regulates the transcription of inflammatory genes involved in the pathogenesis of diabetes, from the early phase to progression and final complications. The NF-κB essential modulator binding domain (NBD) contained in IKKα/β is essential for IKK complex assembly. We therefore investigated the functional consequences of targeting the IKK-dependent NF-κB pathway in the progression of diabetes-associated nephropathy and atherosclerosis.Methods Apolipoprotein E-deficient mice with diabetes induced by streptozotocin were treated with a cell-permeable peptide derived from the IKKα/β NBD region. Kidneys and aorta were analysed for morphology, leucocyte infiltrate, collagen, NF-κB activity and gene expression. In vitro studies were performed in renal and vascular cells. Results NBD peptide administration did not affect the metabolic severity of diabetes but resulted in renal protection, as evidenced by dose-dependent decreases in albuminuria, renal lesions (mesangial expansion, leucocyte infiltration and fibrosis), intranuclear NF-κB activity and proinflammatory and pro-fibrotic gene expression. Furthermore, peptide treatment limited atheroma plaque formation in diabetic mice by decreasing the content of lipids, leucocytes and cytokines and increasing plaque stability markers. This nephroprotective and anti-atherosclerotic effect was accompanied by a decline in systemic T helper 1 cytokines. In vitro, NBD peptide prevented IKK assembly/activation, p65 nuclear translocation, NF-κB-regulated gene expression and cell proliferation induced by either high glucose or inflammatory stimulation. Conclusions/interpretation Peptide-based inhibition of IKK complex formation attenuates NF-κB activation, suppresses inflammation and retards the progression of renal and vascular injury in diabetic mice, thus providing a feasible approach against diabetes inflammatory complications.

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Section: Resultsmentioning

confidence: 99%

Peptide-based inhibition of IκB kinase/nuclear factor-κB pathway protects against diabetes-associated nephropathy and atherosclerosis in a mouse model of type 1 diabetes

et al. 2015

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“…Studies in animal models as well as in humans have revealed that the expression of proinflammatory cytokines such as IL-6 and TGF-α is elevated and sustained by hyper glycemia [31,32] . An excessive inflammatory response has been accepted as a major contributing factor to periodontal tissue destruction and alveolar bone loss.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol ameliorates experimental periodontitis in diabetic mice through negative regulation of TLR4 signaling

et al. 2014

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Aim: To investigate the therapeutic effects of resveratrol (RSV) on periodontitis in diabetic mice and to explore the underlying mechanisms in vitro. Methods: Experimental periodontitis was induced in db/db mice by ligature application of porphyromonas gingivalis. The mice were treated with RSV (20 mg/kg, po) daily for 4 weeks. Alveolar bone loss, proinflammatory cytokines and TLR4 expression in the gingival tissue were measured. Cultured gingival epithelial cells (GECs) were used for in vitro studies. The transcriptional activity of TLR4 downstream signaling was analyzed using Western blotting. Results: RSV administration significantly decreased the blood glucose levels, and ameliorated alveolar bone loss in db/db mice with experimental periodontitis. RSV administration also suppressed the high levels of IL-1β, IL-6, IL-8, TNF-α, and TLR4 in gingival tissue of the mice. In the GECs incubated in high glucose medium, TLR4 expression was substantially upregulated, which was partly blocked in the presence of RSV. Lipopolysaccharides markedly increased the expression and secretion of IL-1β, IL-6, IL-8, and TNF-α in the GECs cultured in high glucose medium, which was also partly blocked in the presence of RSV. Furthermore, RSV significantly suppressed the phosphorylation of TLR4 downstream factors NF-κB p65, p38MAPK, and STAT3. Conclusion: RSV exerts protective effects against experimental periodontitis in db/db mice via negative regulation of TLR4 signaling.

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“…Patients with DM are characterized by a state of chronic inflammation and abnormal activation of the innate immune system . Various inflammatory factors, such as monocyte chemoattractant protein‐1 (MCP‐1), tumor necrotic factor‐ α (TNF‐ α ), and C‐reactive protein (CRP) are upregulated in DM, and may play pivotal roles in the development of CVD in DM patients . Recently, gut microbiota were found to be related to obesity, metabolic endotoxemia, and low‐grade chronic inflammation .…”

Section: Introductionmentioning

confidence: 99%

“…[7][8][9][10][11][12] Various inflammatory factors, such as monocyte chemoattractant protein-1 (MCP-1), tumor necrotic factor-α (TNF-α), and C-reactive protein (CRP) are upregulated in DM, and may play pivotal roles in the development of CVD in DM patients. [13][14][15][16] Recently, gut microbiota were found to be related to obesity, metabolic endotoxemia, and low-grade chronic inflammation. [17][18][19][20] Gut microbiota participate in the energy homeostasis of the host by modulating its capacity to harvest energy from given nutrients and in subsequent fat storage, 17 and can be modulated by dietary fiber, polysaccharides, or high-fat diets.…”

Section: Introductionmentioning

confidence: 99%

Acarbose treatment affects the serum levels of inflammatory cytokines and the gut content of bifidobacteria in Chinese patients with type 2 diabetes mellitus

Liu

et al. 2015

Journal of Diabetes

118

113

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Inflammatory Cytokines and the Risk of Cardiovascular Complications in Type 2 Diabetes

Cited by 54 publications

References 22 publications

Peptide-based inhibition of IκB kinase/nuclear factor-κB pathway protects against diabetes-associated nephropathy and atherosclerosis in a mouse model of type 1 diabetes

Peptide-based inhibition of IκB kinase/nuclear factor-κB pathway protects against diabetes-associated nephropathy and atherosclerosis in a mouse model of type 1 diabetes

Resveratrol ameliorates experimental periodontitis in diabetic mice through negative regulation of TLR4 signaling

Acarbose treatment affects the serum levels of inflammatory cytokines and the gut content of bifidobacteria in Chinese patients with type 2 diabetes mellitus

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