IL-6 and type 1 diabetes mellitus: T cell responses and increase in IL-6 receptor surface expression

Gomes, Karina Braga

doi:10.21037/atm.2016.12.74

Cited by 23 publications

(11 citation statements)

References 18 publications

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“…Elevated levels of inflammatory biomarkers like TNF-α and IL-6 are suggestive of active inflammatory diseases such as T1DM (Gomes, 2017), T2DM (Kasznicki et al, 2012), and vascular injury (Mu et al, 2015), and the aorta is a known target of both T1DM and T2DM in humans and animals (Turkbey et al, 2013;McCulloch et al, 2015;Hagensen et al, 2017). These reports are in agreement with our findings (Fig.…”

Section: Discussionsupporting

confidence: 92%

“…Dyslipidemia is regarded as a risk factor for the development and progression of hypertension (Yoshimura et al, 2011) and vascular injury (Rafieian-Kopaei et al, 2014). Abdominal obesity is a criterion of the metabolic syndrome, also called pre-diabetes, which is a cluster of abnormalities characterized by insulin resistance, inflammation, oxidative stress, hypertension and dyslipidaemia which affects up to 25 % of the population over the age of 50, and carries increased risk of type-2 diabetes mellitus, cardiovascular disease, nonalcoholic fatty liver disease and cancer (Kopelman, 2000;Eckel et al, 2005;Grattagliano et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Vanadium Inhibits Type 2 Diabetes Mellitus-Induced Aortic Ultrastructural Alterations Associated with the Inhibition of Dyslipidemia and Biomarkers of Inflammation in Rats

et al. 2020

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The potential inhibitory effect of the insulin mimicking agent, vanadium on type 2 diabetes mellitus (T2DM)induced alterations to the aorta ultrastructure associated with the suppression of dyslipedima and biomarkers of inflammation has not been investigated before. Therefore, we tested whether vanadium can protect against aortic injury induced secondary to T2DM possibly via the inhibition of blood lipid and inflammatory biomarkers. T2DM was induced in rats by a high-fat diet and streptozotocin (50 mg/ kg), and the treatment group started vanadium treatment five days post diabetic induction and continued until being sacrificed at week 10. Using light and electron microscopy examinations, we observed in the model group substantial damage to the aorta tissue such as damaged endothelium, degenerative cellular changes with vacuolated cytoplasm and thickened internal elastic lamina that were substantially ameliorated by vanadium. Administration of vanadium to diabetic rats also significantly (p<0.05) reduced blood levels of glucose, hyperlipidemia and biomarkers of inflammation (TNF-a, IL-6). We conclude that vanadium protects against T2DM-induced aortic ultrastructural damage in rats, which is associated with the inhibition of blood sugar and lipid and inflammatory biomarkers.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Vanadium Inhibits Type 2 Diabetes Mellitus-Induced Aortic Ultrastructural Alterations Associated with the Inhibition of Dyslipidemia and Biomarkers of Inflammation in Rats

et al. 2020

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“…The data showed that IL-6 is a multifunctional cytokine involved in the inflammatory response and is correlated with insulin-resistant states. Moreover, increased IL-6 levels can predict disease progression in patients with diabetes (Gomes 2017). Studies in Wistar rats have shown that diabetes in adult animals leads to IL-6 overexpression (Feng et al 2018) in the hippocampus and, as our study indicates, maternal diabetes may exert a similar effect in the brains of offspring.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory Consequences of Maternal Diabetes on the Offspring Brain: a Hippocampal Organotypic Culture Study

et al. 2019

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Gestational diabetes is a disorder associated with abnormal chronic inflammation that poses a risk to the developing fetus. We investigated the effects of experimentally induced diabetes (streptozotocin model) in Wistar female rats on the inflammatory status of the hippocampi of their offspring. Additionally, the impact of antidiabetic drugs (metformin and glyburide) on inflammatory processes was evaluated. Organotypic hippocampal cultures (OHCs) were prepared from the brains of the 7-day-old rat offspring of control and diabetic mother rats. On the 7th day in vitro, the cultures were pretreated with metformin (3 μM) or glyburide (1 μM) and then stimulated for 24 h with lipopolysaccharide (LPS, 1 μg/ml). The OHCs obtained from the offspring of diabetic mothers were characterized by the increased mortality of cells and an enhanced susceptibility to damage caused by LPS. Although we showed that LPS stimulated the secretion of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) in the control and diabetic cultures, the levels of IL-1β and IL-6 in the OHC medium obtained from the offspring of diabetic mothers were more pronounced. In the diabetic cultures, enhanced levels of TLR-4 and the overactivation of the NLRP3 inflammasome were demonstrated. Metformin and glyburide pretreatment normalized the LPS-induced IL-1β secretion in the control and diabetic cultures. Furthermore, glyburide diminished both: LPS-induced IL-6 and TNF-α secretion in the control and diabetic cultures and increased NF-κB p65 subunit phosphorylation. Glyburide also diminished the levels of the NLRP3 subunit and caspase-1, but only in the diabetic cultures. The results showed that maternal diabetes affected inflammatory processes in the offspring brain and increased hippocampal sensitivity to the LPS-induced inflammatory response. The use of antidiabetic agents, especially glyburide, had a beneficial impact on the changes caused by maternal diabetes.

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“…The increased concentration of soluble IL6R may be suggestive of metabolic syndrome and insulin resistance in T1D patients ( 25 ). The increase in IL6 signaling observed in T1D patients ( 26 , 27 ) modulates immune response through the expansion of pathogenic Th17 cells and inhibition of generation of Foxp3 + T-regulatory cells is associated with T1D autoimmunity ( 28 – 30 ). It has been shown that Th17 cells contribute to inflammation during chronic kidney progression ( 31 ).…”

Section: Discussionmentioning

confidence: 99%

Proteins of TNF-α and IL6 Pathways Are Elevated in Serum of Type-1 Diabetes Patients with Microalbuminuria

et al. 2018

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Soluble cytokine receptors may play an important role in development of microalbuminuria (MA) in type-1 diabetes (T1D). In this study, we measured 12 soluble receptors and ligands from TNF-α/IL6/IL2 pathways in T1D patients with MA (n = 89) and T1D patients without MA (n = 483) participating in the PAGODA study. Twelve proteins in the sera from T1D patients with and without MA were measured using multiplex Luminex assays. Ten serum proteins (sTNFR1, sTNFR2, sIL2Rα, MMP2, sgp130, sVCAM1, sIL6R, SAA, CRP, and sICAM1) were significantly elevated in T1D patients with MA. After adjusting for age, duration of diabetes, and sex in logistic regression, association remained significant for seven proteins. MA is associated with increasing concentrations of all 10 proteins, with the strongest associations observed for sTNFR1 (OR = 108.3, P < 10−32) and sTNFR2 (OR = 65.5, P < 10−37), followed by sIL2Rα (OR = 12.9, P < 10−13), MMP2 (OR = 5.5, P < 10−6), sgp130 (OR = 5.2, P < 10−3), sIL6R (OR = 4.6, P < 10−4), and sVCAM1 (OR = 3.3, P < 10−4). We developed a risk score system based on the combined odds ratios associated with each quintile for each protein. The risk scores cluster MA patients into three subsets, each associated with distinct risk for MA attributable to proteins in the TNF-α/IL6 pathway (mean OR = 1, 13.5, and 126.3 for the three subsets, respectively). Our results suggest that the TNF-α/IL6 pathway is overactive in approximately 40% of the MA patients and moderately elevated in the middle 40% of the MA patients. Our results suggest the existence of distinct subsets of MA patients identifiable by their serum protein profiles.

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IL-6 and type 1 diabetes mellitus: T cell responses and increase in IL-6 receptor surface expression

Cited by 23 publications

References 18 publications

Vanadium Inhibits Type 2 Diabetes Mellitus-Induced Aortic Ultrastructural Alterations Associated with the Inhibition of Dyslipidemia and Biomarkers of Inflammation in Rats

Vanadium Inhibits Type 2 Diabetes Mellitus-Induced Aortic Ultrastructural Alterations Associated with the Inhibition of Dyslipidemia and Biomarkers of Inflammation in Rats

Inflammatory Consequences of Maternal Diabetes on the Offspring Brain: a Hippocampal Organotypic Culture Study

Proteins of TNF-α and IL6 Pathways Are Elevated in Serum of Type-1 Diabetes Patients with Microalbuminuria

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