Role of Interleukin-6 in Development of Insulin Resistance and Type 2 Diabetes Mellitus

Rehman, Kanwal; Akash, Muhammad Sajid Hamid; Liaqat, Aamira; Kamal, Shagufta; Qadir, Muhammad Imran; Rasul, Akhtar

doi:10.1615/critreveukaryotgeneexpr.2017019712

Cited by 215 publications

(142 citation statements)

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“…A further peculiarity of AD has emerged by its relationship to brain insulin resistance, which was shown to represent an early event in the AD etiology . Insulin resistance, which is a hallmark of type 2 diabetes, has a strong relationship to low‐grade, sterile inflammation, as shown, for example, by substantial upregulation of IL‐6, and activation of the NLRP3 inflammasome . Whether brain insulin resistance has consequences similar to those in type 2 diabetes, or whether it may represent a separate type of pathology referred to as type 3 diabetes, remains to be a matter of debate.…”

Section: Melatonin and Inflammation In Neurodegenerative Diseasesmentioning

confidence: 99%

Melatonin and inflammation—Story of a double‐edged blade

Hardeland

2018

Journal of Pineal Research

327

332

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Melatonin is an immune modulator that displays both pro‐ and anti‐inflammatory properties. Proinflammatory actions, which are well documented by many studies in isolated cells or leukocyte‐derived cell lines, can be assumed to enhance the resistance against pathogens. However, they can be detrimental in autoimmune diseases. Anti‐inflammatory actions are of particular medicinal interest, because they are observed in high‐grade inflammation such as sepsis, ischemia/reperfusion, and brain injury, and also in low‐grade inflammation during aging and in neurodegenerative diseases. The mechanisms contributing to anti‐inflammatory effects are manifold and comprise various pathways of secondary signaling. These include numerous antioxidant effects, downregulation of inducible and inhibition of neuronal NO synthases, downregulation of cyclooxygenase‐2, inhibition of high‐mobility group box‐1 signaling and toll‐like receptor‐4 activation, prevention of inflammasome NLRP3 activation, inhibition of NF‐κB activation and upregulation of nuclear factor erythroid 2‐related factor 2 (Nrf2). These effects are also reflected by downregulation of proinflammatory and upregulation of anti‐inflammatory cytokines. Proinflammatory actions of amyloid‐β peptides are reduced by enhancing α‐secretase and inhibition of β‐ and γ‐secretases. A particular role in melatonin's actions seems to be associated with the upregulation of sirtuin‐1 (SIRT1), which shares various effects known from melatonin and additionally interferes with the signaling by the mechanistic target of rapamycin (mTOR) and Notch, and reduces the expression of the proinflammatory lncRNA‐CCL2. The conclusion on a partial mediation by SIRT1 is supported by repeatedly observed inhibitions of melatonin effects by sirtuin inhibitors or knockdown.

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Section: Melatonin and Inflammation In Neurodegenerative Diseasesmentioning

confidence: 99%

Melatonin and inflammation—Story of a double‐edged blade

Hardeland

2018

Journal of Pineal Research

327

332

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“…9 Akt also phosphorylates a pivotal regulatory molecules in glucose metabolism, 10 and phosphorylation of some of these regulatory substrates is defective in cases of IR. 10 Other pathophysiological mechanisms associated with MS and obesity are the adipocytokines, signaling factors overproduced from the hypertrophied adipocytes, 11 such as pro-inflammatory interleukin-6 (IL-6), 12 interleukin-17 (IL-17) 13 and tumor necrosis factor -alpha (TNF-α). 14 Furthermore, Adipocyte dysfunctions impair the secretion of adiponectin which plays important roles not only in appetite and satiety regulation but also in insulin sensitivity and secretion, inflammation, expenditure of energy and endothelial function.…”

Section: Introductionmentioning

confidence: 99%

Alagebrium Mitigates Metabolic Insults in High Carbohydrate and High Fat Diet Fed Wistar Rats

et al. 2020

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Background: Metabolic syndrome (MS) is characterized by sustained hyperglycemia that triggers advanced glycation end products (AGEs) generation. Alagebrium (ALA) is an advanced glycation end products (AGEs) cross-links breaker.Methods: 32 Wistar rats were divided into normal control (NC) group (8 rats) and MS groups (24 rats) received a high carbohydrate high fat diet (HCFD) for 10 weeks. Rats with established MS were equally divided into 3 subgroups remained on HCFD for further 6 weeks: MS control (MSC), ALA treated received 10 mg/kg/day ALA orally and metformin treated (MF) (a reference drug) received 50 mg/kg/day MF orally. The studied parameters were systolic blood pressure (SBP), body and liver weights (BW, LW), LW/BW% ratio, fasting blood glucose (FBG), serum insulin, lipid profile, liver enzymes, serum AGEs, hepatic Interleukin-17 (IL-17), adipokines, pAkt/Akt ratio, and liver histopathology. Results: HCFD elevated SBP, BW, LW and LW/BW% ratio, FBG, serum insulin, and AGEs. It also deteriorated lipid profile and liver enzymes, induced inflammation, insulin resistance and histopathological derangements. ALA ameliorated the elevated SBP, FBG, lipid profile, liver enzymes, mitigated insulin resistance, hepatic IL-17, serum AGEs, modulated adipokines levels and improved liver histopathology. However, MF had better effects than ALA in all studied parameters except AGEs. Conclusion: ALA is protective against dietary-induced MS via ameliorating the inflammatory process and serum AGEs that implicated in MS pathogenesis, which makes it a promising new tool in MS treatment.

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“…Interleukin-6 (IL-6) is a proinflammatory cytokine that conclusively motivates the progression of IR and the pathogenesis of T2DM through the generation of inflammation by controlling differentiation, migration, proliferation, and cell apoptosis [33]. The presence of IL-6 in tissues is a normal consequence, but its irregular generation and long-term exposure leads to the development of inflammation, which stimulates IR and overt T2DM [33]. A mechanistic association occurs between the promotion of IL-6 and IR.…”

Section: Introductionmentioning

confidence: 99%

The immune-opioid axis in prediabetes: prediction of prediabetes with insulin resistance by plasma interleukin-10 and Endomorphin-2 to kappa-opioid receptors ratio

Moustafa¹

2020

Preprint

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BackgroundPrediabetes is characterized by a hemoglobin A1c of 5.7%–6.4% and fasting blood glucose of 100–125 mg/dl. A high percentage of prediabetes subjects develops into type 2 diabetes mellitus in the following years. The effect of opioid peptides and their receptors, in addition to immunological cytokines on prediabetes, is not well understood.ObjectiveWe hypothesize that opioid peptides and their receptors affect the insulin and the insulin resistance (IR) in patients with prediabetes and that the immune cytokines, IL-6 (inflammatory factor) and IL-10 (anti-inflammatory factor), influence the opioid system.MethodsA total of 60 patients with prediabetes and IR (prediabetes+IR), 60 patients with prediabetes without IR (prediabetes-IR), and 60 controls participated in the study. The IR state was HOMAIR > 2.5. The enzyme linked immunosorbent assay was used to measure interleukin (IL)-6, IL-10, μ- and κ-opioid receptors (MOR and KOR), endomorphin-2 (EM2), and β- endorphin (βEP).ResultsThe subjects with prediabetes had dyslipidemia, and not all of them underwent the IR state. The IL-6, IL-10, β-endorphin, MOR, and endomorphin-2 were higher in the prediabetes subgroups compared with the control group. MOR was correlated with IL-10 and KOR. Prediabetes+IR can be predicted by the increased levels of the combination of IL-10, βEP, and EM2 and by the combination of IL-10 and endomorphin-2/KOR with good sensitivity and specificity.ConclusionOpioid peptides and their receptors were upregulated in patients with prediabetes depending on the significance of IR. These changes in the opioid system depend on the immune cytokines. Both systems need to be normalized to prevent further development into diabetes mellitus.

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Role of Interleukin-6 in Development of Insulin Resistance and Type 2 Diabetes Mellitus

Cited by 215 publications

References 0 publications

Melatonin and inflammation—Story of a double‐edged blade

Melatonin and inflammation—Story of a double‐edged blade

Alagebrium Mitigates Metabolic Insults in High Carbohydrate and High Fat Diet Fed Wistar Rats

The immune-opioid axis in prediabetes: prediction of prediabetes with insulin resistance by plasma interleukin-10 and Endomorphin-2 to kappa-opioid receptors ratio

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