scholarly journals The Diethylcarbamazine Delays and Decreases the NETosis of Polymorphonuclear Cells of Humans with DM Type 2

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Juan C. Segoviano-Ramirez ◽  
Daniel F. Lopez-Altamirano ◽  
Jaime Garcia-Juarez ◽  
Juan E. S. Aguirre-Garza ◽  
Eloy Cárdenas-Estrada ◽  
...  
Keyword(s):  
Metabolic Diseases ◽  
Innate Immune ◽  
High Morbidity ◽  
Polymorphonuclear Cells ◽  
Expected Time ◽  
Human Volunteers ◽  
Plantar Ulcers ◽  
Dm Type 2

Type 2 diabetes mellitus (DM2) is a disease that reports high morbidity and mortality rates worldwide. Between its complications, one of the most important is the development of plantar ulcers. The role of the polymorphonuclear cells (PMNs) is affected by metabolic diseases like DM2. Fifteen years ago, reports about a new mechanism of innate immune response where PMNs generate some kind of webs with their chromatin were published. This mechanism was called NETosis. Also, some researchers have demonstrated that NETosis is responsible for the delay of the ulcer healing both in patients with DM2 and in animal models of DM2. Purified PMNs from healthy and DM2 human volunteers were incubated with diethylcarbamazine (DEC) and then induced to NETosis using phorbol 12-myristate 13-acetate (PMA). In a randomized blind study model, the NETosis was documented by confocal microscopy. On microphotographs, the area of each extracellular neutrophil trap (NET) formed at different times after stimuli with PMA was bounded, and the intensity of fluorescence (IF) from the chromatin dyed with 4′,6-diamidino-2-phenylindole dihydrochloride (DAPI) was quantified. PMNs from healthy volunteers showed the development of NETs at expected times according to the literature. The same phenomenon was seen in cultures of PMNs from metabolically controlled DM2 volunteers. The use of DEC one hour before of the challenge with PMA delayed the NETosis in both groups. The semiquantitative morphometric analysis of the IF from DAPI, as a measure of PMN’s capacity to forming NETs, is consistent with these results. The ANOVA test demonstrated that NETosis was lower and appeared later than expected time, both in PMNs from healthy (p≤0.000001) and from DM2 (p≤0.000477) volunteers. In conclusion, the DEC delays and decreases the NETosis by PMNs from healthy as well as DM2 people.

scholarly journals SEVELAMER CARBONATE MODULATES THE NLRP3 AND NLRP6 INFLAMMASOME EXPRESSION IN PATIENTS WITH DIABETIC NEPHROPATHY

2021 ◽  
Vol 80 (2) ◽  
pp. 125-132
Author(s):  
Grațiela Grădișteanu Pîrcălăbioru ◽  
Mariana-Carmen Chifiriuc ◽  
Roxana Adriana Stoica
Keyword(s):  
Diabetic Nephropathy ◽  
Nlrp3 Inflammasome ◽  
Treatment Plan ◽  
Innate Immune ◽  
Pentraxin 3 ◽  
Quantitative Real Time Pcr ◽  
Blood Samples ◽  
Sevelamer Carbonate

Interaction of microorganisms with the host innate immune system is a crucial factor that could modify diabetes and its associated complications. Recent reports have elucidated the role of NLRP3 inflammasome in diabetes, but to our knowledge there is no data regarding the role of other inflammasomes in diabetes-induced inflammation. To investigate this, blood samples were collected from type 2 diabetes (T2DM) patients with nephropathy as well as from healthy volunteers. After red blood cell lysis, RNA was isolated from all collected blood samples. The expression of NLRP 6, NLRP3, ASC, PRO-IL1Β, and PRO-IL18 was assessed by quantitative Real Time PCR (qRT-PCR). Patients with diabetic nephropathy showed higher NLRP3 inflammasome expression compared to healthy controls whereas no significant differences were observed in case of NLRP6 inflammasome. In addition, Pentraxin 3 expression was elevated in patients with diabetic nephropathy. A detailed analysis of the patient’s clinical data revealed the fact that subjects receiving sevelamer carbonate in their treatment plan harboured low expression of Pentraxin 3 (PTX3) and NLRP3 associated genes.

scholarly journals Adipocytes, Innate Immunity and Obesity: A Mini-Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Alecia M. Blaszczak ◽  
Anahita Jalilvand ◽  
Willa A. Hsueh
Keyword(s):  
Adipose Tissue ◽  
Immune System ◽  
Immune Cells ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Lymphoid Cells ◽  
Innate Immune Cells ◽  
Adaptive Immune

The role of adipose tissue (AT) inflammation in obesity and its multiple related-complications is a rapidly expanding area of scientific interest. Within the last 30 years, the role of the adipocyte as an endocrine and immunologic cell has been progressively established. Like the macrophage, the adipocyte is capable of linking the innate and adaptive immune system through the secretion of adipokines and cytokines; exosome release of lipids, hormones, and microRNAs; and contact interaction with other immune cells. Key innate immune cells in AT include adipocytes, macrophages, neutrophils, and innate lymphoid cells type 2 (ILC2s). The role of the innate immune system in promoting adipose tissue inflammation in obesity will be highlighted in this review. T cells and B cells also play important roles in contributing to AT inflammation and are discussed in this series in the chapter on adaptive immunity.

scholarly journals The role of selected mechanisms of innate immunity in the pathogenesis of diabetes

2021 ◽  
Vol 11 (9) ◽  
pp. 544-549
Author(s):  
Paulina Trojanowska ◽  
Magdalena Chrościńska-Krawczyk ◽  
Alina Trojanowska ◽  
Ewa Tywanek ◽  
Jakub Wronecki ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Metabolic Diseases ◽  
Inflammatory Diseases ◽  
The Body ◽  
Low Grade ◽  
Intracellular Space ◽  
Cytoplasmic Proteins

Understanding the important role of the non-specific immune response in protecting the body against the development of numerous diseases has become partially possible after the discovery of several classes of pattern recognition receptors (PRR), such as Toll-like or NOD-like receptors. A group of cytoplasmic proteins called the inflammasome, which detect PAMP and DAMP through the PRR receptors, is able to activate pro-inflammatory cytokines and trigger an acute inflammatory reaction both in the extracellular and intracellular space. Low-grade systemic and local inflammation contributes to the development and progression of various conditions, including autoimmune and metabolic diseases, such as diabetes, metabolic syndrome and atherosclerosis, which until recently were not even considered inflammatory diseases. This review will discuss the role of innate immunity in the development of type 1 and type 2 diabetes, focusing on the role of specific innate immunity receptors and insulin resistance involved in these diseases pathogenesis.

scholarly journals Defective liver glycogen autophagy related to hyperinsulinemia in intrauterine growth-restricted newborn wistar rats

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Juan de Toro-Martín ◽  
Tamara Fernández-Marcelo ◽  
Águeda González-Rodríguez ◽  
Fernando Escrivá ◽  
Ángela M. Valverde ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Metabolic Diseases ◽  
Critical Role ◽  
Liver Glycogen ◽  
Hormonal Control ◽  
Standard Diet ◽  
Major Organ ◽  
Mtorc1 Pathway

Abstract Maternal malnutrition plays a critical role in the developmental programming of later metabolic diseases susceptibility in the offspring, such as obesity and type 2 diabetes. Because the liver is the major organ that produces and supplies blood glucose, we aimed at defining the potential role of liver glycogen autophagy in the programming of glucose metabolism disturbances. To this end, newborns were obtained from pregnant Wistar rats fed ad libitum with a standard diet or 65% food-restricted during the last week of gestation. We found that newborns from undernourished mothers showed markedly high basal insulin levels whereas those of glucagon were decreased. This unbalance led to activation of the mTORC1 pathway and inhibition of hepatic autophagy compromising the adequate handling of glycogen in the very early hours of extrauterine life. Restoration of autophagy with rapamycin but not with glucagon, indicated no defect in autophagy machinery per se, but in signals triggered by glucagon. Taken together, these results support the notion that hyperinsulinemia is an important mechanism by which mobilization of liver glycogen by autophagy is defective in food-restricted animals. This early alteration in the hormonal control of liver glycogen autophagy may influence the risk of developing metabolic diseases later in life.

scholarly journals Physical Exercise as Therapy for Type 2 Diabetes Mellitus: From Mechanism to Orientation

2019 ◽  
Vol 74 (4) ◽  
pp. 313-321 ◽  
Author(s):  
Dan Yang ◽  
Yifan Yang ◽  
Yanlin Li ◽  
Rui Han
Keyword(s):  
Type 2 Diabetes ◽  
Exercise Therapy ◽  
Metabolic Diseases ◽  
Whole Body ◽  
Mechanism Study ◽  
Physiological Mechanisms ◽  
Glycolipid Metabolism ◽  
Randomized Controlled Studies

Background: Exercise therapy plays an important role in the prevention and treatment of type 2 diabetes (T2DM). The mechanism of exercise therapy in the improvement of glycolipid metabolism of T2DM is very complex and not completely clear. Summary: Exercise training improves the whole body metabolic health in patients with T2DM, leading to an increase in glycolipid uptake and utilization, improved insulin sensitivity, optimized body mass index, and modulated DNA methylation, etc. Recent findings support that some cytokines such as irisin, osteocalcin, and adiponectin are closely related to exercise and metabolic diseases. This study briefly reviews the physiological mechanisms of exercise therapy in diabetes and the potential role of these cytokines in exercise. Key Messages: More high-quality, targeted, randomized controlled studies are needed urgently, from mechanism study to treatment direction, to provide a more theoretical basis for exercise therapy and to explore new therapeutic targets for diabetes.

scholarly journals Perturbations to Homeostasis in Experimental Models Revealed Innate Pathways Driving Food Allergy

2020 ◽  
Vol 11 ◽  
Author(s):  
Kelly Bruton ◽  
Joshua F. E. Koenig ◽  
Allyssa Phelps ◽  
Manel Jordana
Keyword(s):  
Food Allergy ◽  
Critical Role ◽  
Allergic Sensitization ◽  
Experimental Models ◽  
Innate Immune ◽  
Th2 Response ◽  
Type 2 Immune Response ◽  
Physical And Chemical

While type 2 immunity has been conventionally viewed as beneficial against helminths, venoms, and poisons, and harmful in allergy, contemporary research has uncovered its critical role in the maintenance of homeostasis. The initiation of a type 2 immune response involves an intricate crosstalk between structural and immune cells. Structural cells react to physical and chemical tissue perturbations by secreting alarmins, which signal the innate immune system to restore homeostasis. This pathway acts autonomously in the context of sterile injury and in the presence of foreign antigen initiates an adaptive Th2 response that is beneficial in the context of venoms, toxins, and helminths, but not food allergens. The investigation of the triggers and mechanisms underlying food allergic sensitization in humans is elusive because sensitization is a silent process. Therefore, the central construct driving food allergy modeling is based on introducing perturbations of tissue homeostasis along with an allergen which will result in an immunological and clinical phenotype that is consistent with that observed in humans. The collective evidence from multiple models has revealed the pre-eminent role of innate cells and molecules in the elicitation of allergic sensitization. We posit that, with the expanding use of technologies capable of producing formidable datasets, models of food allergy will continue to have an indispensable role to delineate mechanisms and establish causal relationships.

scholarly journals MECHANISMS IN ENDOCRINOLOGY: Gut microbiota in patients with type 2 diabetes mellitus

2015 ◽  
Vol 172 (4) ◽  
pp. R167-R177 ◽  
Author(s):  
Kristine H Allin ◽  
Trine Nielsen ◽  
Oluf Pedersen
Keyword(s):  
Type 2 Diabetes ◽  
Gut Microbiota ◽  
Metabolic Diseases ◽  
Short Chain Fatty Acids ◽  
Intestinal Content ◽  
Low Grade ◽  
Bacterial Fermentation ◽  
Underlying Mechanisms

Perturbations of the composition and function of the gut microbiota have been associated with metabolic disorders including obesity, insulin resistance and type 2 diabetes. Studies on mice have demonstrated several underlying mechanisms including host signalling through bacterial lipopolysaccharides derived from the outer membranes of Gram-negative bacteria, bacterial fermentation of dietary fibres to short-chain fatty acids and bacterial modulation of bile acids. On top of this, an increased permeability of the intestinal epithelium may lead to increased absorption of macromolecules from the intestinal content resulting in systemic immune responses, low-grade inflammation and altered signalling pathways influencing lipid and glucose metabolism. While mechanistic studies on mice collectively support a causal role of the gut microbiota in metabolic diseases, the majority of studies in humans are correlative of nature and thus hinder causal inferences. Importantly, several factors known to influence the risk of type 2 diabetes, e.g. diet and age, have also been linked to alterations in the gut microbiota complicating the interpretation of correlative studies. However, based upon the available evidence, it is hypothesised that the gut microbiota may mediate or modulate the influence of lifestyle factors triggering development of type 2 diabetes. Thus, the aim of this review is to critically discuss the potential role of the gut microbiota in the pathophysiology and pathogenesis of type 2 diabetes.

scholarly journals PPARδActivity in Cardiovascular Diseases: A Potential Pharmacological Target

PPAR Research ◽  
2009 ◽  
Vol 2009 ◽  
pp. 1-9 ◽  
Author(s):  
Angela Tesse ◽  
Ramaroson Andriantsitohaina ◽  
Thierry Ragot
Keyword(s):  
Metabolic Diseases ◽  
Peroxisome Proliferator ◽  
In Vivo Models ◽  
Pharmacological Target ◽  
Cardiovascular Cells ◽  
Peroxisome Proliferator Activated Receptors

Activation of peroxisome proliferator-activated receptors (PPARs), and particularly of PPARαand PPARγ, using selective agonists, is currently used in the treatment of metabolic diseases such as hypertriglyceridemia and type 2 diabetes mellitus. PPARαand PPARγanti-inflammatory, antiproliferative and antiangiogenic properties in cardiovascular cells were extensively clarified in a variety of in vitro and in vivo models. In contrast, the role of PPARδin cardiovascular system is poorly understood. Prostacyclin, the predominant prostanoid released by vascular cells, is a putative endogenous agonist for PPARδ, but only recently PPARδselective synthetic agonists were found, improving studies about the physiological and pathophysiological roles of PPARδactivation. Recent reports suggest that the PPARδactivation may play a pivotal role to regulate inflammation, apoptosis, and cell proliferation, suggesting that this transcriptional factor could become an interesting pharmacological target to regulate cardiovascular cell apoptosis, proliferation, inflammation, and metabolism.

Retinol binding protein 4 and its membrane receptors: a metabolic perspective

2015 ◽  
Vol 22 (1) ◽  
Author(s):  
Ronja Fedders ◽  
Matthias Muenzner ◽  
Michael Schupp
Keyword(s):  
Metabolic Diseases ◽  
Binding Protein ◽  
Current Data ◽  
Membrane Receptors ◽  
Retinol Binding Protein ◽  
Metabolic Effects ◽  
Retinol Binding Protein 4 ◽  
Underlying Mechanisms

AbstractNearly a decade of intense research has passed since the first report linking circulating retinol binding protein 4 (RBP4) to the development of insulin resistance. By now, a variety of underlying mechanisms have been identified; some of them are adherent to the canonical role of this circulating protein, which is to transport and deliver retinol to target tissues, and others that seem rather independent of retinol transport. Despite all these efforts, a consensus in the basic principles of RBP4’s metabolic effects has not been reached and some controversy remains. Using this as an opportunity, we here review and discuss current data on RBP4’s action on insulin sensitivity and its dependency on retinol homeostasis. We pay special attention to the involvement of RBP4 membrane receptors that were identified during these years, such as ‘stimulated by retinoic acid 6’ (STRA6), and whose identification added another layer of complexity to RBP4’s diverse actions. A better understanding of RBP4’s functions might allow its therapeutic exploitations, urgently needed in our period that is defined by an epidemic increase in metabolic diseases such as obesity and type 2 diabetes.

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