High IL-1α production was induced in the WBN/Kob-Leprfa type 2 diabetes mellitus rat model and inhibited by Syphacia muris infection

Summary The novel WBN/Kob-Leprfa (fa/fa) congenic rat strain is considered a useful rat model of type 2 diabetes mellitus (T2DM). Accumulating findings suggest that low-grade inflammation is a causative factor in T2DM and that circulating levels of inflammatory cytokines are associated with insulin resistance. However, inflammatory cytokine profiles and their correlations with T2DM development/progression in fa/fa rats have not been studied. In this study, we found that the fa/fa rats had considerably high plasma levels of interleukin (IL)-1α. Abundant cecal IL-1α mRNA expression and cecal inflammation with infiltrating IL-1α-producing macrophages was observed in fa/fa rats. Bone marrow derived macrophages from fa/fa rats expressed high levels of IL-1α upon lipopolysaccharide stimulation. Furthermore, Syphacia muris infection, which delays the onset of T2DM, reduced both plasma and cecal IL-1α levels in fa/fa rats. These results suggest that macrophage infiltration and IL-1α secretion comprise an important part of T2DM development and that S. muris infection inhibits pro-inflammatory cytokine expression in fa/fa rats.

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Role of TLR4/MyD88/NF-κB signaling in heart and liver-related complications in a rat model of type 2 diabetes mellitus

Journal of International Medical Research ◽

10.1177/0300060521997590 ◽

2021 ◽

Vol 49 (3) ◽

pp. 030006052199759

Author(s):

Jiajia Tian ◽

Yanyan Zhao ◽

Lingling Wang ◽

Lin Li

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Signaling Pathway ◽

Rat Model ◽

Fasting Blood Glucose ◽

Diabetic Rats ◽

Primary Response ◽

Monocyte Chemoattractant Protein 1

Aims To analyze expression of members of the Toll-like receptor (TLR)4/myeloid differentiation primary response 88 (MyD88)/nuclear factor (NF)-κB signaling pathway in the heart and liver in a rat model of type 2 diabetes mellitus (T2DM). Our overall goal was to understand the underlying pathophysiological mechanisms. Methods We measured fasting blood glucose (FBG) and insulin (FINS) in a rat model of T2DM. Expression of members of the TLR4/MyD88/NF-κB signaling pathway as well as downstream cytokines was investigated. Levels of mRNA and protein were assessed using quantitative real-time polymerase chain reaction and western blotting, respectively. Protein content of tissue homogenates was assessed using enzyme-linked immunosorbent assays. Results Diabetic rats had lower body weights, higher FBG, higher FINS, and higher intraperitoneal glucose tolerance than normal rats. In addition, biochemical indicators related to heart and liver function were elevated in diabetic rats compared with normal rats. TLR4 and MyD88 were involved in the occurrence of T2DM as well as T2DM-related heart and liver complications. TLR4 caused T2DM-related heart and liver complications through activation of NF-κB. Conclusions TLR4/MyD88/NF-κB signaling induces production of tumor necrosis factor-α, interleukin-6, and monocyte chemoattractant protein-1, leading to the heart- and liver-related complications of T2DM.

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High Plasma Levels of Gremlin-1 and Macrophage Migration Inhibitory Factor, but Not Their Ratio, Indicate an Increased Risk for Acute Coronary Syndrome in Patients With Type 2 Diabetes Mellitus

Clinical Cardiology ◽

10.1002/clc.22509 ◽

2016 ◽

Vol 39 (4) ◽

pp. 201-206 ◽

Cited By ~ 7

Author(s):

Karin A.L. Müller ◽

Dominik Rath ◽

Martina Schmid ◽

Heiko Schoenleber ◽

Meinrad Gawaz ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Acute Coronary Syndrome ◽

Macrophage Migration Inhibitory Factor ◽

High Plasma ◽

Macrophage Migration ◽

Coronary Syndrome ◽

Increased Risk

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Combined Effects of a Dietary Fiber Mixture and Wheat Albumin in a Rat Model of Type 2 Diabetes Mellitus

Journal of Nutritional Science and Vitaminology ◽

10.3177/jnsv.62.416 ◽

2016 ◽

Vol 62 (6) ◽

pp. 416-424

Author(s):

Kazuhiro KUBO ◽

Ayano KOIDO ◽

Misako KITANO ◽

Hirotaka YAMAMOTO ◽

Morio SAITO

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Dietary Fiber ◽

Rat Model ◽

Combined Effects

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Exenatide prevents diabetic nephropathy in a rat model of type 2 diabetes mellitus (fat-fed and streptozotocin-treated rats)

Scientific Journal of October 6 University ◽

10.21608/sjou.2017.30448 ◽

2017 ◽

Vol 4 (1) ◽

pp. 9-19

Author(s):

Tarek Motawi ◽

Hanan Abdelgawad ◽

Shaymaa Galal ◽

Sherine Rizk

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Diabetic Nephropathy ◽

Rat Model

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Role of Circulating Microparticles in Type 2 Diabetes Mellitus: Implications for Pathological Clotting

Seminars in Thrombosis and Hemostasis ◽

10.1055/s-0041-1740150 ◽

2021 ◽

Author(s):

Siphosethu Cassandra Maphumulo ◽

Etheresia Pretorius

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Systemic Inflammation ◽

Blood Cells ◽

Low Grade ◽

Chronic Hyperglycemia ◽

Increased Risk

AbstractType 2 diabetes mellitus (T2DM) is a multifactorial chronic metabolic disease characterized by chronic hyperglycemia due to insulin resistance and a deficiency in insulin secretion. The global diabetes pandemic relates primarily to T2DM, which is the most prevalent form of diabetes, accounting for over 90% of all cases. Chronic low-grade inflammation, triggered by numerous risk factors, and the chronic activation of the immune system are prominent features of T2DM. Here we highlight the role of blood cells (platelets, and red and white blood cells) and vascular endothelial cells as drivers of systemic inflammation in T2DM. In addition, we discuss the role of microparticles (MPs) in systemic inflammation and hypercoagulation. Although once seen as inert by-products of cell activation or destruction, MPs are now considered to be a disseminated storage pool of bioactive effectors of thrombosis, inflammation, and vascular function. They have been identified to circulate at elevated levels in the bloodstream of individuals with increased risk of atherothrombosis or cardiovascular disease, two significant hallmark conditions of T2DM. There is also general evidence that MPs activate blood cells, express proinflammatory and coagulant effects, interact directly with cell receptors, and transfer biological material. MPs are considered major players in the pathogenesis of many systemic inflammatory diseases and may be potentially useful biomarkers of disease activity and may not only be of prognostic value but may act as novel therapeutic targets.

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