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Inflammation and type 2 diabetes

Tomáš Vaisar, Erica Couzens, Arnold Hwang, Michael Russell, Carolyn E Barlow, Laura F DeFina, Andrew N Hoofnagle, Francis Kim
AIMS/HYPOTHESIS: One of the hallmarks of diabetes is impaired endothelial function. Previous studies showed that HDL can exert protective effects on endothelium stimulating NO production and protecting from inflammation and suggested that HDL in obese people with diabetes and dyslipidemia may have lower endothelial protective function. We aimed to investigate whether type 2 diabetes impairs HDL endothelium protective functions in people with otherwise normal lipid profile. METHODS: In a case-control study (n = 41 per group) nested in the Cooper Center Longitudinal Study we tested the ability of HDL to protect endothelium by stimulating endothelial nitric oxide synthase activity and suppressing NFκB-mediated inflammatory response in endothelial cells...
2018: PloS One
Paola Cipriani, Vasiliky Liakouli, Francesco Carubbi, Onorina Berardicurti, Paola Di Benedetto, Francesco Ciccia, Giuliana Guggino, Saverio Alvaro, Giovanni Triolo, Roberto Giacomellia, Piero Ruscitti
BACKGROUND: Although in the past, prevention of the joint destruction and disability were strongly emphasised in rheumatoid arthritis (RA), at present, a growing body of evidence is focused at identifying the best management of associated comorbidities, such as type 2 diabetes (T2D). Recently, the hypothesis that blocking pro-inflammatory activity may be helpful in the treatment of some comorbidities has been proposed in RA patients. OBJECTIVE: We reviewed the role of IL-1β during RA and T2D, the efficacy of IL-1 blocking agents in controlling both diseases and, possible, decreasing the concomitant enhanced atherosclerotic process...
March 13, 2018: Reviews on Recent Clinical Trials
Davide Di Fusco, Vincenzo Dinallo, Ivan Monteleone, Federica Laudisi, Irene Marafini, Eleonora Franzè, Antonio Di Grazia, Rami Dwairi, Alfredo Colantoni, Angela Ortenzi, Carmine Stolfi, Giovanni Monteleone
Metformin, a hypoglycemic drug used for treatment of type 2 diabetes, regulates also inflammatory pathways. By using several models of intestinal inflammation, we examined whether metformin exerts anti-inflammatory effects and investigated the basic mechanism by which metformin blocks pathologic signals. Colitic mice given metformin exhibited less colonic inflammation and increased expression of active AMP-activated protein kinase, a mediator of the metabolic effects of metformin, in both epithelial and lamina propria compartments...
March 14, 2018: Clinical Science (1979-)
Muneeb U Rehman, Shahzada Mudasir Rashid, Saiema Rasool, Sheeba Shakeel, Bilal Ahmad, Sheikh Bilal Ahmad, Hassan Madkhali, Majid Ahmad Ganaie, Sabiya Majid, Showkat Ahmad Bhat
Development of diabetic nephropathy (DN) is directly linked to oxidative stress and inflammation. In this context, inflammatory and oxidative markers have gained much attention as targets for therapeutic intervention. We studied the effect of zingerone in a streptozotocin/high fat diet (STZ/HFD)-induced type 2 diabetic Wistar rat model. Zingerone also known as vanillyl acetone is a pharmacologically active compound present usually in dry ginger. STZ/HFD caused excessive increase in ROS and inflammation in experimental animals...
March 14, 2018: Archives of Physiology and Biochemistry
Yi Huang, Hua Jiang, Yun Chen, Xiaqiong Wang, Yanqing Yang, Jinhui Tao, Xianming Deng, Gaolin Liang, Huafeng Zhang, Wei Jiang, Rongbin Zhou
The dysregulation of NLRP3 inflammasome can cause uncontrolled inflammation and drive the development of a wide variety of human diseases, but the medications targeting NLRP3 inflammasome are not available in clinic. Here, we show that tranilast (TR), an old anti-allergic clinical drug, is a direct NLRP3 inhibitor. TR inhibits NLRP3 inflammasome activation in macrophages, but has no effects on AIM2 or NLRC4 inflammasome activation. Mechanismly, TR directly binds to the NACHT domain of NLRP3 and suppresses the assembly of NLRP3 inflammasome by blocking NLRP3 oligomerization...
March 12, 2018: EMBO Molecular Medicine
Tianyi Qiu, Min Li, Miles A Tanner, Yan Yang, James R Sowers, Ronald J Korthuis, Michael A Hill
BACKGROUND: Accumulation of multiple subtypes of immune cells in perivascular adipose tissue (PVAT) has been proposed to cause vascular inflammation and dysfunction in type 2 diabetes (T2DM). This study was designed to investigate specific roles for dendritic cells in PVAT in the development of vascular inflammation and impaired PVAT-mediated vasorelaxation in T2DM. METHODS AND RESULTS: Studies were performed using db/db mice (model of T2DM) and their Db heterozygote (DbHET), lean and normoglycemic controls...
March 9, 2018: Metabolism: Clinical and Experimental
Jessica M Skeie, Benjamin T Aldrich, Andrew S Goldstein, Gregory A Schmidt, Cynthia R Reed, Mark A Greiner
The objective of this study was to characterize the proteome of the corneal endothelial cell layer and its basement membrane (Descemet membrane) in humans with various severities of type II diabetes mellitus compared to controls, and identify differentially expressed proteins across a range of diabetic disease severities that may influence corneal endothelial cell health. Endothelium-Descemet membrane complex tissues were peeled from transplant suitable donor corneas. Protein fractions were isolated from each sample and subjected to multidimensional liquid chromatography and tandem mass spectrometry...
2018: PloS One
Mitsugu Shimobayashi, Verena Albert, Bettina Woelnerhanssen, Irina C Frei, Diana Weissenberger, Anne Christin Meyer-Gerspach, Nicolas Clement, Suzette Moes, Marco Colombi, Jerome A Meier, Marta M Swierczynska, Paul Jenö, Christoph Beglinger, Ralph Peterli, Michael N Hall
Obesity is a major risk factor for insulin resistance and type 2 diabetes. In adipose tissue, obesity-mediated insulin resistance correlates with the accumulation of proinflammatory macrophages and inflammation. However, the causal relationship of these events is unclear. Here, we report that obesity-induced insulin resistance in mice precedes macrophage accumulation and inflammation in adipose tissue. Using a mouse model that combines genetically induced, adipose-specific insulin resistance (mTORC2-knockout) and diet-induced obesity, we found that insulin resistance causes local accumulation of proinflammatory macrophages...
March 12, 2018: Journal of Clinical Investigation
Kelsey H Collins, Walter Herzog, Graham Z MacDonald, Raylene A Reimer, Jaqueline L Rios, Ian C Smith, Ronald F Zernicke, David A Hart
Inflammation can arise in response to a variety of stimuli, including infectious agents, tissue injury, autoimmune diseases, and obesity. Some of these responses are acute and resolve, while others become chronic and exert a sustained impact on the host, systemically, or locally. Obesity is now recognized as a chronic low-grade, systemic inflammatory state that predisposes to other chronic conditions including metabolic syndrome (MetS). Although obesity has received considerable attention regarding its pathophysiological link to chronic cardiovascular conditions and type 2 diabetes, the musculoskeletal (MSK) complications (i...
2018: Frontiers in Physiology
Gaia Botteri, Laia Salvadó, Anna Gumà, D Lee Hamilton, Paul J Meakin, Gemma Montagut, Michael L J Ashford, Victoria Ceperuelo-Mallafré, Sonia Fernández-Veledo, Joan Vendrell, María Calderón-Dominguez, Dolors Serra, Laura Herrero, Javier Pizarro, Emma Barroso, Xavier Palomer, Manuel Vázquez-Carrera
OBJECTIVE: β-secretase/β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) is a key enzyme involved in Alzheimer's disease that has recently been implicated in insulin-independent glucose uptake in myotubes. However, it is presently unknown whether BACE1 and the product of its activity, soluble APPβ (sAPPβ), contribute to lipid-induced inflammation and insulin resistance in skeletal muscle cells. MATERIALS/METHODS: Studies were conducted in mouse C2C12 myotubes, skeletal muscle from Bace1-/- mice and mice treated with sAPPβ and adipose tissue and plasma from obese and type 2 diabetic patients...
March 8, 2018: Metabolism: Clinical and Experimental
Christian Herder, Andreas Schmitt, Florian Budden, André Reimer, Bernhard Kulzer, Michael Roden, Thomas Haak, Norbert Hermanns
BACKGROUND: Depressive disorders represent a frequent comorbidity of type 1 diabetes (T1D) and type 2 diabetes (T2D). Subclinical inflammation increases the risk of depressive symptoms in the general population, but the relationship appears complex and bidirectional, and longitudinal data from patients with diabetes are lacking. Therefore, this study aimed to analyse associations between changes in depressive symptoms and changes in biomarkers of inflammation in patients with T1D and T2D and to investigate the hypothesis that higher baseline levels of biomarkers of inflammation are related to a less pronounced reduction of depressive symptoms over time...
March 6, 2018: Psychoneuroendocrinology
Ivana Novak, Anna Solini
Type 2 diabetes is reaching an alarming prevalence worldwide. Its complex pathogenesis certainly includes a pivotal role of low-grade inflammation, which could be triggered by excessive purinergic signaling. In this complex scenario, extracellular ATP impairs the function of two key players: β-cell and adipose tissue. In the former, P2Y and possibly some P2X receptors-ion channels regulate insulin secretion, but it is still debated whether excessive ATP can via P2X receptors impair β-cell function directly or whether cell damage is due to an excessive systemic release of cytokines...
March 6, 2018: Current Opinion in Immunology
Dorota Różańska, Bożena Regulska-Ilow
Anthocyanins are food compounds which belong to polyphenols and can mainly be found in dark fruits (e.g., blueberries, black currants, cranberries) and vegetables (e.g., red cabbage, radish, eggplant). The results of large research have shown that these compounds play an important role in the prevention of type 2 diabetes (T2D). In rodent studies and in studies with isolated omental adipocytes, it was observed that anthocyanins regulated the carbohydrate metabolism in the body due to the upregulation of GLUT4 (insulinregulated glucose transporter) translocation, increased activation of PPARγ (peroxisome proliferator-activated receptor-γ) in adipose tissue and skeletal muscles as well as increased secretion of adiponectin and leptin...
January 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
Christian Herder, Andreas Schmitt, Florian Budden, André Reimer, Bernhard Kulzer, Michael Roden, Thomas Haak, Norbert Hermanns
Subclinical inflammation has been implicated in the development of depression, a common comorbidity of type 1 diabetes (T1D) and type 2 diabetes (T2D). This study aimed to characterise the relationships between biomarkers of inflammation and depressive symptoms in T1D and T2D. Biomarkers of inflammation were measured in serum of participants with elevated depressive symptoms and T1D (n = 389, mean age 38 years, diabetes duration 15 ± 11 years) or T2D (n = 204, mean age 56 years, diabetes duration 13 ± 8 years)...
March 9, 2018: Translational Psychiatry
Ivy N Haskins, Julietta Chang, Zubaidah Nor Hanipah, Tavankit Singh, Neal Mehta, Arthur J McCullough, Stacy A Brethauer, Philip R Schauer, Ali Aminian
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) increases the risk of liver cirrhosis and hepatocellular carcinoma and is also strongly correlated with extrahepatic diseases, including cardiovascular disease and type 2 diabetes. This risk of NAFLD among obese individuals who are otherwise metabolically healthy is not well characterized. OBJECTIVES: To determine the prevalence and characteristics of NAFLD in individuals with metabolically healthy obesity. SETTING: A tertiary, academic, referral hospital...
March 2018: Surgery for Obesity and related Diseases: Official Journal of the American Society for Bariatric Surgery
P Zhang, W Zhang, D Zhang, M Wang, R Aprecio, N Ji, O Mohamed, Y Li, Y Ding, Q Wang
BACKGROUND AND OBJECTIVE: Periodontitis is an increasingly prevalent complication of diabetes mellitus (known as diabetes mellitus-associated periodontitis), and 25-hydroxyvitamin D3 (25VD3 ) was recently found to be a critical regulator of innate immunity in this disease, but the underlying mechanisms remain poorly understood. T-cell protein tyrosine phosphatase non-receptor type 2 (PTPN2) is a potential downstream protein of the 25VD3 /vitamin D receptor pathway. The aim of this study was to investigate the regulation of PTPN2 in periodontal inflammation in diabetes mellitus-associated periodontitis...
March 8, 2018: Journal of Periodontal Research
Haoran Wang, Chen Zhu, Ying Ying, Lingyu Luo, Deqiang Huang, Zhijun Luo
Metformin has been used as a glucose lowering drug for several centuries and is now a first-line drug for type 2 diabetes mellitus (T2DM). Since the discovery that it activates AMP-activated protein kinase (AMPK) and reduces risk of cancer, metformin has drawn great attentions. Another drug, berberine, extracted from berberis vulgaris L. (root), was an ancient herbal medicine in treating diarrhea. Ongoing experimental and clinical studies have illuminated great potential of berberine in regulation of glucose and lipid homeostasis, cancer growth and inflammation...
February 9, 2018: Oncotarget
Arpeeta Sharma, Mitchel Tate, Geetha Mathew, James E Vince, Rebecca H Ritchie, Judy B de Haan
It is now increasingly appreciated that inflammation is not limited to the control of pathogens by the host, but rather that sterile inflammation which occurs in the absence of viral or bacterial pathogens, accompanies numerous disease states, none more so than the complications that arise as a result of hyperglycaemia. Individuals with type 1 or type 2 diabetes mellitus (T1D, T2D) are at increased risk of developing cardiac and vascular complications. Glucose and blood pressure lowering therapies have not stopped the advance of these morbidities that often lead to fatal heart attacks and/or stroke...
2018: Frontiers in Physiology
H Qu, Y Qiu, Y Wang, Y Liao, Y Zheng, H Zheng
AIMS: To assess circulating fetuin-B concentrations in subjects with different degrees of glucose tolerance and to analyze the association of fetuin-B concentrations with insulin resistance and the first phase of glucose-stimulated insulin secretion. METHODS: Plasma fetuin-B concentrations were analyzed in 149 subjects with normal glucose tolerance (NGT, n=54), impaired glucose regulation (preDM, n=42) and newly diagnosed type-2 diabetes mellitus (nT2DM, n=53). Intravenous glucose tolerance tests (IVGTTs) and biochemical parameters were also assessed in all participants...
February 22, 2018: Diabetes & Metabolism
Yung-Luen Shih, Hsu-Feng Lu, Chiao-Wan Hsiao, Kuo-Ting Ho, Pei-Chi Chen, Chien-Ning Huang, Yuanmay Chang, Shang-Jyh Kao, Ming-Yuh Shiau, Yih-Hsin Chang
Type 2 diabetes mellitus (T2DM) is associated with chronic inflammation, suggesting the metabolic abnormalities are originated from or exacerbated by cytokine overproduction. Cytokines and counter-regulatory molecules are crucial in keeping the balance of immune responses and, therefore, are potential candidates involved in T2DM etiology, development and complications. Our previous reports identify several significant associations between the genotypes of cytokine genes and T2DM and/or the clinical lipid parameters, which strongly suggest the participation of immune-regulatory molecules in lipid metabolism...
2018: International Journal of Medical Sciences
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