Molecular and cellular mechanisms linking inflammation to insulin resistance and β-cell dysfunction

Epigenetics is involved in the altered expression of gene networks that underlie insulin resistance and insufficiency. Major genes controlling b-cell differentiation and function, such as PAX4, PDX1, and GLP1 receptor, are epigenetically controlled. Epigenetics can cause insulin resistance through immunomediated pro-inflammatory actions related to several factors, such as NF-kB, osteopontin, and Toll-like receptors. Hereafter, we provide a critical and comprehensive summary on this topic with a particular emphasis on translational and clinical aspects. We discuss the effect of epigenetics on b-cell regeneration for cell replacement therapy, the emerging bioinformatics approaches for analyzing the epigenetic contribution to type 2 diabetes mellitus (T2DM), the epigenetic core of the transgenerational inheritance hypothesis in T2DM, and the epigenetic clinical trials on T2DM. Therefore, prevention or reversion of the epigenetic changes occurring during T2DM development may reduce the individual and societal burden of the disease.

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“…1). 40 Recently, evidence began accumulating regarding the epigenetic mechanisms underlying the immunological basis of diabetes and inflammation.…”

Section: B-cell Development and Functionmentioning

confidence: 99%

Clinical relevance of epigenetics in the onset and management of type 2 diabetes mellitus

et al. 2017

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“…T2D which accounts for *90 % of all cases of diabetes is characterized by insulin resistance and b-cell dysfunction [2]. Several factors including genetics, environmental, physical inactivity, and obesity have been suggested to play a role in the development of insulin resistance and b-cell dysfunction.…”

Section: Introductionmentioning

confidence: 99%

Decreased expression of microRNA-21 is associated with increased cytokine production in peripheral blood mononuclear cells (PBMCs) of obese type 2 diabetic and non-diabetic subjects

et al. 2016

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The aim of this study was to investigate the role of miR-21 in inflammatory responses in peripheral blood mononuclear cells (PBMCs) of type 2 diabetic (T2D) and healthy subjects. 20 healthy and 20 T2D subjects were enrolled in the study. miR-21 expression in PBMCs of the subjects was measured using real-time PCR. IL-6 and TNF-α levels in culture supernatants were quantified using ELISA. miR-21 expression was not significantly different between the diabetic and nondiabetic groups. A downregulation of miR-21 expression was observed in PBMCs of obese subjects in both diabetic and nondiabetic groups. In addition, miR-21 expression was negatively correlated with weight, waist circumference, body mass index, and triglyceride in both the diabetic and nondiabetic groups. Our results also demonstrated that the PBMCs of obese subjects significantly secreted a higher level of IL-6 and TNF-α in comparison with the PBMCs of nonobese subjects. Furthermore, a significant inverse correlation between miR-21 expression and TNF-α and IL-6 production from the PBMCs was observed. These data suggest that miR-21 expression is decreased in PBMCs of obese subjects and reduced expression appears to be associated with increased secreted cytokine level in media of PBMCs of obese subjects.

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“…Some studies [7,[21][22][23] have demonstrated the close relationship of obesity, insulin resistance, and inflammation. They showed that adipokines, such as resistin, are molecular links of the action of adipocytes and macrophages [24]. Therefore, resistin might provide a unique link between the risk of obesity, inflammation, and metabolic syndrome in humans [21].…”

Section: Discussionmentioning

confidence: 99%

Beneficial Effects of n-3 Fatty Acids on Cardiometabolic and Inflammatory Markers in Type 2 Diabetes Mellitus: A Clinical Trial

Mazaherioun¹,

Djalali²,

Koohdani³

et al. 2017

Med Princ Pract

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Objective: To determine the effect of supplementation with n-3 polyunsaturated fatty acids (PUFAs) on circulatory resistin and monocyte chemoattractant protein 1 (MCP-1) levels in type 2 diabetes mellitus (T2DM) patients. Subjects and Methods: This was a 10-week, placebo-controlled, double-blind, randomized trial of n-3 PUFAs (2,700 mg/day) versus placebo (soft gels containing 900 mg of edible paraffin). Forty-four T2DM patients were supplemented with n-3 PUFAs and another 44 patients received placebo (3 patients discontinued the trial). Serum resistin, MCP-1, and the lipid profile were measured before and after supplementation. The adiponectin-resistin index (1 + log₁₀ [resistin] - log₁₀ [adiponectin]) and atherogenic index (log₁₀ triglyceride/high-density lipoprotein cholesterol) of plasma (an indicator of cardiovascular complications) were assessed. The independent Student t test was used to assess the differences between the supplement and placebo groups and the paired t test to analyze the before/after changes. Results: In this study, n-3 PUFAs reduced serum MCP-1 levels (from 260.5 to 230.5 pg/mL; p = 0.002), but they remained unchanged in the placebo group. n-3 PUFAs could not decrease serum resistin levels. The adiponectin-resistin index was significantly reduced after supplementation with n-3 PUFAs when compared to the placebo. The atherogenic index was also significantly improved after supplementation with n-3 PUFAs (from 1.459 to 1.412; p = 0.006). Conclusions: TheMCP-1 levels and lipid profile were improved after supplementation with n-3 PUFAs, but resistin serum levels were not changed. Hence, the anti-inflammatory effects of n-3 PUFAs might be mediated by targeting MCP-1.

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Molecular and cellular mechanisms linking inflammation to insulin resistance and β-cell dysfunction

Cited by 231 publications

References 268 publications

Clinical relevance of epigenetics in the onset and management of type 2 diabetes mellitus

Clinical relevance of epigenetics in the onset and management of type 2 diabetes mellitus

Decreased expression of microRNA-21 is associated with increased cytokine production in peripheral blood mononuclear cells (PBMCs) of obese type 2 diabetic and non-diabetic subjects

Beneficial Effects of n-3 Fatty Acids on Cardiometabolic and Inflammatory Markers in Type 2 Diabetes Mellitus: A Clinical Trial

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