One of the crucial proteins to infl uence type 2 diabetes: The high mobility group A1

Aims. To detect the association of C1q/TNF-related protein-3 (CTRP-3) and high-mobility group box-1 (HMGB-1) in subjects with prediabetes (pre-DM) and newly diagnosed type 2 diabetes (nT2DM).Methods. 224 eligible participants were included. The 75 g oral glucose tolerance test (OGTT) and several clinical parameters of metabolic disorders and cytokines were measured. All participants were divided into three groups: normal glucose tolerance (NGT,n=62), pre-DM (n=111), and nT2DM group (n=56).Results. Plasma CTRP-3 concentrations were significantly lower in subjects with pre-DM and nT2DM than that of the NGT group, while plasma HMGB-1 levels were higher in pre-DM and nT2DM group compared with the NGT group (P<0.05). A multiple linear regression analysis showed both plasma CTRP-3 and HMGB-1 concentrations were independently associated with homeostasis model assessment for insulin resistance (HOMA-IR) and interleukin-6 (IL-6) (P<0.05for all). Further multiple logistical regression analyses revealed that both plasma CTRP-3 and HMGB-1 levels were significantly associated with pre-DM and nT2DM after adjusting for several confounders (P<0.001for all).Conclusions. Circulating CTRP-3 and HMGB-1 concentrations might be promising biomarkers to predict prediabetes and type 2 diabetes.

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High-mobility group box 1 contributes to mechanical allodynia and spinal astrocytic activation in a mouse model of type 2 diabetes

Brain Research Bulletin ◽

10.1016/j.brainresbull.2012.03.002 ◽

2012 ◽

Vol 88 (4) ◽

pp. 332-337 ◽

Cited By ~ 43

Author(s):

Peng-Cheng Ren ◽

Yong Zhang ◽

Xu-Dong Zhang ◽

Li-Jun An ◽

Hai-Gang Lv ◽

...

Keyword(s):

Type 2 Diabetes ◽

Mouse Model ◽

Mechanical Allodynia ◽

High Mobility ◽

High Mobility Group

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Paucity of CD34-positive cells and increased expression of high-mobility group box 1 in coronary thrombus with type 2 diabetes mellitus

Atherosclerosis ◽

10.1016/j.atherosclerosis.2012.07.027 ◽

2012 ◽

Vol 224 (2) ◽

pp. 511-514 ◽

Cited By ~ 16

Author(s):

Atsushi Yamashita ◽

Kensaku Nishihira ◽

Yunosuke Matsuura ◽

Takashi Ito ◽

Kouichi Kawahara ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

High Mobility ◽

High Mobility Group ◽

Coronary Thrombus

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Effect of a 6-week Aerobic Exercise Program on High-mobility Group Box 1 Gene Expression in Aortic Tissue of Diabetic Rats

Quarterly of Horizon of Medical Sciences ◽

10.32598/hms.27.1.2378.1 ◽

2021 ◽

Vol 27 (1) ◽

pp. 82-97

Author(s):

Samira Hassanpour Soleimani ◽

◽

Asiyeh Abbassi Daloii ◽

Ahmed Abdi ◽

Sheerin Zilaei Bori ◽

...

Keyword(s):

Gene Expression ◽

Type 2 Diabetes ◽

Aerobic Exercise ◽

Exercise Program ◽

High Mobility ◽

Diabetic Rats ◽

High Mobility Group ◽

Male Rats ◽

Aortic Tissue

Aims: Type 2 diabetes is a rising problem and a significant risk factor for small and large vessel disease. The present study aims to investigate the effect of a 6-week aerobic exercise program on High-mobility Group Box 1 (HMGB1) gene expression in aortic tissue of diabetic rats. Methods & Materials: In this experimental study, 40 male rats aged 8 weeks were randomly selected. Once familiarized with the exercise protocol, they were divided into four groups of healthy-control (n=10), diabetic-control (n=10), healthy-exercise (n=10), and diabetic-exercise (n=10). Type 2 diabetes was first induced, and then the rats run on a treadmill for 6 weeks, 5 sessions per week. After 12-14 h of fasting and 72 h after the last session, aortic tissue sampling was performed for HMGB1 analysis by quantitative real-time polymerase chain reaction (q-RT PCR) technique. Data analysis was performed using 1-way ANOVA and Tukey post hoc test at the significant level of P<0.05. Findings: Induction of type 2 diabetes led to a significant increase in HMGB1 gene expression in rats (P=0.001), significantly reduced following aerobic exercise (P=0.003). Aerobic exercise also reduced the expression of the HMGB1 gene in healthy rats (P=0.000). Conclusion: Aerobic exercise may have a protective effect by reducing the HMGB1 gene expression in the aortic tissue of diabetic rats. It can be used as an effective non-pharmacological method to improve diabetes-induced inflammation and prevent vascular disorders.

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Analysis of HMGB-1 level before and after providing atorvastatin standard therapy in coronary artery disease patients with type-2 diabetes mellitus compared to without type-2 diabetes mellitus

Journal of Basic and Clinical Physiology and Pharmacology ◽

10.1515/jbcpp-2020-0442 ◽

2021 ◽

Vol 32 (4) ◽

pp. 439-446

Author(s):

Widya Handayani ◽

Suharjono ◽

Mohammad Yogiarto

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Coronary Artery Disease ◽

Type 2 Diabetes Mellitus ◽

Coronary Artery ◽

High Mobility ◽

Pleiotropic Effect ◽

Serum Samples ◽

Artery Disease

Abstract Objectives Coronary artery disease (CAD) is one of the main causes of death from cardiovascular disease, because heart attacks result in atherosclerosis which causes narrowing of the arteries. Atorvastatin has a pleiotropic effect as anti-inflammatory through one of the target levels of High Mobility Group Box-1 (HMGB-1). This prospective observational study aimed to analyze the effect of atorvastatin on serum HMGB-1 levels in CAD. Methods Samples were collected from prospective observation pre–post study in May–July 2018 with consecutive sampling method. Serum HMGB-1 levels were measured in patients with CAD who were given atorvastatin for CAD with type-2 diabetes mellitus compared without type-2 diabetes mellitus in a patient ward. Blood was collected on admission day and before the patient left the hospital. After centrifugation, serum samples were stored at −80 °C before measurement. We used an ELISA kit (IBL International) to determine HMGB-1 concentrations. This research protocol has been approved by the Ethical Committee of Dr. Soetomo General Hospital, Surabaya. Results We enrolled 38 patients and divided them into two groups which 19 patients on CAD with type-2 diabetes mellitus and 19 patients without diabetes mellitus. Serum HMGB-1 levels in CAD with type-2 diabetes mellitus were increased significantly (p = 0.049) and not significantly decreased in CAD without type-2 diabetes mellitus (p = 0.480). The HMGB-1 level was not significantly different between the two groups (p = 0.210). Conclusions HMGB-1 levels after providing atorvastatin in CAD with type-2 diabetes mellitus increased significantly, meanwhile, in CAD without type-2 diabetes mellitus did not decrease significantly. The HMGB-1 level was not significantly different between the two groups. Longer time and more point for the collected sample needed for further research.

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High-mobility group box-1 protein from CC10+ club cells promotes type 2 response in the later stage of respiratory syncytial virus infection

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00552.2017 ◽

2019 ◽

Vol 316 (1) ◽

pp. L280-L290 ◽

Cited By ~ 4

Author(s):

Sisi Chen ◽

Guangyuan Yu ◽

Jun Xie ◽

Wei Tang ◽

Leiqiong Gao ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

High Mobility ◽

Clinical Severity ◽

High Mobility Group ◽

Hmgb1 Protein ◽

Club Cells ◽

Hmgb1 Expression ◽

Syncytial Virus ◽

Tract Infections

The type 2 immune response, induced by infection of respiratory syncytial virus (RSV), has been linked to asthma development, but it remains unclear how the response is initiated. Here, we reported that the high-mobility group box-1 (HMGB1) protein promotes the type 2 response in the later stage of RSV infection. In mice, we found that type 2 cytokines were elevated in the later stages, which were strongly diminished after administration of anti-HMGB1 antibodies. Further investigation revealed that HMGB1 expression was localized to CC10+ club cells in the lung. In the clinic, levels of HMGB1 in nasopharyngeal aspirates in hospitalized infants with RSV bronchiolitis [median (interquartile range) 161.20 ng/ml (68.06–221.30)] were significantly higher than those without lower respiratory tract infections [21.94 ng/ml (12.12–59.82); P < 0.001]. Moreover, higher levels of HMGB1 correlated with clinical severity. These results reveal a link between viral infection and the asthma-like type 2 responses that are associated with long-term consequences.

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High Mobility Group Box 1 and Dickkopf-Related Protein 1 as New Biomarkers of Type 2 Diabetes Mellitus: Associations with Increased Glucose Toxicity and Atherogenicity and Lower β Cell Function

10.20944/preprints202006.0011.v1 ◽

2020 ◽

Author(s):

Hussein Kadhem Al-Hakeim ◽

Qasim Jasim Al-Kaabi ◽

Michael Maes

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Beta Cell ◽

Beta Cell Function ◽

Cell Function ◽

High Mobility ◽

Related Protein ◽

Glucose Toxicity ◽

Wnt Pathways

Background: Type 2 diabetes mellitus (T2DM) is associated with increased atherogenicity and inflammatory responses, which may be related to increased levels of high mobility group box 1 (HMGB1) and Dickkopf-related protein 1 (DKK1). Objective: The role of HMGB1 and DKK1 in T2DM is examined in association with lipid and insulin profiles. Methods: Serum HMGB1 and DKK1 were measured in T2DM with and without hypertension and compared with controls. Results: HMGB1 and DKK1 are significantly higher in T2DM irrespective of hypertension. T2DM was also accompanied by increased atherogenicity indices. HMGB1 and DKK1 are significantly correlated with HbA1c, glucose, indices of insulin resistance, β-cell function, and glucose toxicity, and different atherogenic indices. A large part of the variance in the β-cell index (30.5%) and glucose toxicity (34.8%) was explained by the combined effects of HMGB1 and DKK1 and hypertension. We found that 18.3% of the variance of the atherogenic index of plasma was explained by HMGB1 and DKK1 levels and that 31.2% was explained by glucose toxicity, HMGB1 and body weight. Conclusion: The higher serum HMGB1 and DKK1 levels in T2DM patients and the associations with atherogenicity indicate that low grade inflammation and disorders in the Wnt pathways are associated with T2DM and that both HMGB1 and DKK1 may contribute to increased atherogenicity in T2DM. Moreover, both biomarkers may cause more deficits in β-cell function and increase glucose toxicity leading to the development of more inflammation and diabetic complications. HMGB1 and the Wnt pathways are new drug targets in the treatment of T2DM.

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Hp1-1 as a Genetic Marker Regulating Inflammation and the Possibility of Developing Diabetic Complications in Patients with Type 2 Diabetes—Cohort Studies

Genes ◽

10.3390/genes11111253 ◽

2020 ◽

Vol 11 (11) ◽

pp. 1253

Author(s):

Anna Stempkowska ◽

Magdalena Walicka ◽

Edward Franek ◽

Marek Naruszewicz ◽

Mariusz Panczyk ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Genetic Marker ◽

High Mobility ◽

Postprandial Glucose ◽

Interleukin 10 ◽

Soluble Form ◽

Diabetic Patients ◽

Haptoglobin Phenotype

Background: This study assessed the influence of the haptoglobin phenotype on markers regulating inflammation in patients with type 2 diabetes. Methods: The haptoglobin phenotypes, soluble form of CD163 receptor (sCD163), p53 concentrations and high mobility group box protein 1 (HMGB1), interleukin 10 (IL-10) secretion in serum were assayed via ELISA tests. In the first part of the project, patients were divided into three groups which differed by the haptoglobin phenotype, and afterwards into two groups according to the criterion of the presence or absence of cardiovascular disease. Results: Diabetic patients with haptoglobin phenotype 1-1 (Hp1-1) had a significantly higher concentration of IL-10 and sCD163 compared to haptoglobin phenotype 2-1 (Hp2-1) and haptoglobin phenotype 2-2 (Hp2-2). Moreover, diabetic patients with Hp1-1 had a significantly lower concentration of p53 and HMGB1 compared to diabetic patients with Hp2-1 and Hp2-2. The results have shown that diabetics with Hp2-1 had a significantly lower postprandial glucose level compared to diabetics with Hp2-2. Apart from that, there were no differences in the occurrence of haptoglobin variants between patients with or without cardiovascular disease. Conclusions: Our study provides new data for a relationship between the type of haptoglobin in patients with type 2 diabetes and the concentration of factors that regulate the body’s inflammation. We have shown that the Hp1-1 can serve as a genetic marker of inflammatory processes.

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High-Mobility Group Box 1 Protein Signaling in Painful Diabetic Neuropathy

International Journal of Molecular Sciences ◽

10.3390/ijms21030881 ◽

2020 ◽

Vol 21 (3) ◽

pp. 881 ◽

Cited By ~ 6

Author(s):

Vikram Thakur ◽

Jayanarayanan Sadanandan ◽

Munmun Chattopadhyay

Keyword(s):

Diabetic Neuropathy ◽

Active Form ◽

High Mobility ◽

High Mobility Group ◽

Receptor Protein ◽

Diabetic Patients ◽

Hmgb1 Protein ◽

Painful Neuropathy ◽

Type 2 Diabetic

Diabetes is a global epidemic and more than 50% diabetic patients are also diagnosed with neuropathy, which greatly affects the quality of life of the patients. Available treatments are not always successful due to the limited efficacy and complications, such as addiction and dependency. Studies have implicated that high mobility group box1 (HMGB1) protein plays a crucial role in neuroinflammation and the development of neuropathic conditions. HMGB1 is a proinflammatory cytokine that can be released from necrotic cells in passive form or in response to inflammatory signals as an active form. HMGB1 is the ligand for the receptor for advanced glycation end products (RAGE), and toll-like receptors, (TLR)-2 and TLR4, which also indirectly activates C-X-C chemokine receptor type 4 (CXCR4). We investigated whether blocking of HMGB1 can reduce pain and inflammation in diabetic neuropathic animals to further understand the role of HMGB1 in diabetic neuropathy. Type 2 diabetic rats and mice were treated with natural inhibitor of HMGB1, glycyrrhizin (GLC) for five days/week for four weeks at a dose of 50 mg/kg per day by intraperitoneal injection. The animals were divided into three categories: naïve control, diabetic alone, diabetic with GLC treatment. All of the behavioral analyses were conducted before and after the treatment. The expression of inflammatory markers and changes in histone acetylation in the peripheral nervous system were measured by immunohistochemistry and Western blot analysis after the completion of the treatment. Our study revealed that TLR4, HMGB1, CXCR4, and Nod-like receptor protein 3 (NLRP3) levels were increased in the spinal and dorsal root ganglia (DRG) neurons of Type 2 diabetic mice and rats with painful neuropathy. GLC treatment inhibited the increases in TLR4, NLRP3, and CXCR4 expressions and improved the mechanical and thermal pain threshold in these animals. Immunohistochemical studies revealed that hyperglycemia mediated inflammation influenced HMGB1 acetylation and its release from the neurons. It also altered histone 3 acetylation in the microglial cells. The inhibition of HMGB1 by GLC prevented the release of HMGB1 as well as H3K9 acetylation. These findings indicate that the interruption of HMGB1 mediated inflammation could ameliorate diabetic neuropathy and might exhibit a unique target for the treatment.

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