scholarly journals Cellular Stresses and Stress Responses in the Pathogenesis of Insulin Resistance

2018 ◽  
Vol 2018 ◽  
pp. 1-27 ◽  
Author(s):  
Arnold N. Onyango
Keyword(s):  
Insulin Resistance ◽  
Stress Responses ◽  
Environmental Pollutants ◽  
Stress Generation ◽  
Target Cells ◽  
Inflammasome Activation ◽  
Related Factor ◽  
The Metabolic Syndrome ◽  
Cellular Stresses ◽  
The Unfolded Protein Response

Insulin resistance (IR), a key component of the metabolic syndrome, precedes the development of diabetes, cardiovascular disease, and Alzheimer’s disease. Its etiological pathways are not well defined, although many contributory mechanisms have been established. This article summarizes such mechanisms into the hypothesis that factors like nutrient overload, physical inactivity, hypoxia, psychological stress, and environmental pollutants induce a network of cellular stresses, stress responses, and stress response dysregulations that jointly inhibit insulin signaling in insulin target cells including endothelial cells, hepatocytes, myocytes, hypothalamic neurons, and adipocytes. The insulin resistance-inducing cellular stresses include oxidative, nitrosative, carbonyl/electrophilic, genotoxic, and endoplasmic reticulum stresses; the stress responses include the ubiquitin-proteasome pathway, the DNA damage response, the unfolded protein response, apoptosis, inflammasome activation, and pyroptosis, while the dysregulated responses include the heat shock response, autophagy, and nuclear factor erythroid-2-related factor 2 signaling. Insulin target cells also produce metabolites that exacerbate cellular stress generation both locally and systemically, partly through recruitment and activation of myeloid cells which sustain a state of chronic inflammation. Thus, insulin resistance may be prevented or attenuated by multiple approaches targeting the different cellular stresses and stress responses.

scholarly journals Molecular Mechanisms of Insulin Resistance Development

2014 ◽  
Vol 17 (2) ◽  
pp. 29-40 ◽  
Author(s):  
Vsevolod Arsen'evich Tkachuk ◽  
Alexander Vyacheslavovich Vorotnikov
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Blood Glucose ◽  
Molecular Mechanisms ◽  
The Body ◽  
Target Cells ◽  
Endocrine Regulation ◽  
High Blood Glucose ◽  
Alcoholic Fatty Liver ◽  
The Metabolic Syndrome

Insulin resistance (IR) is a phenomenon associated with an impaired ability of insulin to stimulate glucose uptake by target cells and to reduce the blood glucose level. A response increase in insulin secretion by the pancreas and hyperinsulinemia are compensatory reactions of the body. The development of IR leads to the inability of target cells to respond to insulin that results in developing type 2 diabetes mellitus (T2DM) and metabolic syndrome. For this reason, the metabolic syndrome is defined in practice as a combination of IR with one or more pathologies such as T2DM, arterial hypertension, dyslipidemia, abdominal obesity, non-alcoholic fatty liver disease, and some others. However, a combination of high blood glucose and insulin levels always serves as its physiological criterion. IR should be considered as a systemic failure of the endocrine regulation in the body. Physiological causes of IR are diverse. The main ones are nutritional overload and accumulation of certain lipids and their metabolites in cells, low physical activity, chronic inflammation and stress of various nature, including oxidative and endoplasmic reticulum stress (impairment of damaged protein degradation in the cell). Recent studies have demonstrated that these physiological mechanisms likely act through a single intracellular scenario. This is the impairment of signal transduction from the insulin receptor to its targets via the negative feedback mechanism in intracellular insulin-dependent signaling cascades. This review describes the physiological and intracellular mechanisms of insulin action and focuses on their abnormalities upon IR development. Finally, feasible trends in early molecular diagnosis and therapy of IR are discussed.

Metabolic Syndrome During Menopause

2019 ◽  
Vol 17 (6) ◽  
pp. 595-603 ◽  
Author(s):  
Sezcan Mumusoglu ◽  
Bulent Okan Yildiz
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Central Obesity ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
Natural Menopause ◽  
The Metabolic Syndrome ◽  
Increased Risk ◽  
Aging Women

The metabolic syndrome (MetS) comprises individual components including central obesity, insulin resistance, dyslipidaemia and hypertension and it is associated with an increased risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). The menopause per se increases the incidence of MetS in aging women. The effect(s) of menopause on individual components of MetS include: i) increasing central obesity with changes in the fat tissue distribution, ii) potential increase in insulin resistance, iii) changes in serum lipid concentrations, which seem to be associated with increasing weight rather than menopause itself, and, iv) an association between menopause and hypertension, although available data are inconclusive. With regard to the consequences of MetS during menopause, there is no consistent data supporting a causal relationship between menopause and CVD. However, concomitant MetS during menopause appears to increase the risk of CVD. Furthermore, despite the data supporting the association between early menopause and increased risk of T2DM, the association between natural menopause itself and risk of T2DM is not evident. However, the presence and the severity of MetS appears to be associated with an increased risk of T2DM. Although the mechanism is not clear, surgical menopause is strongly linked with a higher incidence of MetS. Interestingly, women with polycystic ovary syndrome (PCOS) have an increased risk of MetS during their reproductive years; however, with menopausal transition, the risk of MetS becomes similar to that of non-PCOS women.

C-Peptide and its Correlation to Parameters of Insulin Resistance in the Metabolic Syndrome

2011 ◽  
Vol 10 (8) ◽  
pp. 921-927 ◽  
Author(s):  
Shaheena Banu ◽  
Nasimudeen R. Jabir ◽  
C. N. Manjunath ◽  
Shazi Shakil ◽  
Mohammad A. Kamal
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
C Peptide ◽  
The Metabolic Syndrome

scholarly journals Very similar cardiometabolic profile in the moderate and high cardiovascular risk classes: a population-based study

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
M Chlabicz ◽  
J Jamolkowski ◽  
W Laguna ◽  
P Sowa ◽  
M Paniczko ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Cardiovascular Disease ◽  
Cardiovascular Risk ◽  
High Risk ◽  
Population Based ◽  
Low Risk ◽  
Public Institution ◽  
Population Based Study ◽  
The Metabolic Syndrome ◽  
Cardiometabolic Profile

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Medical University of Bialystok, Poland Background Cardiovascular disease (CVD) is a major, worldwide problem and remain the dominant cause of premature mortality in the word. Simultaneously the metabolic syndrome is a growing problem. The aim of this study was to investigate the cardiometabolic profile among cardiovascular risk classes, and to estimate CV risk using various calculators. Methods The longitudinal, population-based study, was conducted in 2017-2020. A total of 931 individuals aged 20-79 were included. Anthropometric and biochemical profiles were measured according to a standardized protocols. The study population was divided into CV risk classes according to the latest recommendation. Comparisons variables between subgroups were conducted using Dwass-Steele-Critchlow-Fligner test. To estimate CV risk were used: the  Systematic Coronary Risk Estimation system, Framingham Risk Score and LIFEtime-perspective model for individualizing CardioVascular Disease prevention strategies in apparently healthy people (LIFE-CVD). Results The mean age was 49.1± 15.5 years, 43.2% were male. Percentages of low-risk, moderate-risk, high-risk and very-high CV risk were 46.1%, 22.8%, 13.5%, 17.6%, respectively. Most of the analyzed anthropometric, body composition and laboratory parameters did not differ between the moderate and high CV risk participants, whereas the low risk group differed significantly. In the moderate and high-risk groups, abdominal distribution of adipose tissue dominated with significantly elevated parameters of insulin resistance. Interestingly, estimating lifetime risk of myocardial infarction, stroke or CV death using LIFE-CVD calculator yielded similar results in moderate and high CV risk classes. Conclusion The participants belonging to moderate and high CV risk classes have a very similar unfavorable cardiometabolic profile which may result in the similar lifetime CV risk. This may imply the need for more aggressive pharmacological and non-pharmacological management of CV risk factors in the moderate CV risk population. It would be advisable to consider combining the moderate and high risk classes into one high CV risk class, or it may be worth adding one of the parameters of abdominal fat distribution to the CV risk calculators as an expression of increased insulin resistance. Abstract Figure 1.

scholarly journals Combined In Vitro and In Vivo Approaches to Propose a Putative Adverse Outcome Pathway for Acute Lung Inflammation Induced by Nanoparticles: A Study on Carbon Dots

Nanomaterials ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 180
Author(s):  
Maud Weiss ◽  
Jiahui Fan ◽  
Mickaël Claudel ◽  
Luc Lebeau ◽  
Françoise Pons ◽  
...  
Keyword(s):  
Carbon Dots ◽  
Lung Inflammation ◽  
Adverse Outcome ◽  
Cellular Responses ◽  
Target Cells ◽  
Inflammasome Activation ◽  
Adverse Outcome Pathway ◽  
Acute Lung Inflammation

With the growth of nanotechnologies, concerns raised regarding the potential adverse effects of nanoparticles (NPs), especially on the respiratory tract. Adverse outcome pathways (AOP) have become recently the subject of intensive studies in order to get a better understanding of the mechanisms of NP toxicity, and hence hopefully predict the health risks associated with NP exposure. Herein, we propose a putative AOP for the lung toxicity of NPs using emerging nanomaterials called carbon dots (CDs), and in vivo and in vitro experimental approaches. We first investigated the effect of a single administration of CDs on mouse airways. We showed that CDs induce an acute lung inflammation and identified airway macrophages as target cells of CDs. Then, we studied the cellular responses induced by CDs in an in vitro model of macrophages. We observed that CDs are internalized by these cells (molecular initial event) and induce a series of key events, including loss of lysosomal integrity and mitochondrial disruption (organelle responses), as well as oxidative stress, inflammasome activation, inflammatory cytokine upregulation and macrophage death (cellular responses). All these effects triggering lung inflammation as tissular response may lead to acute lung injury.

scholarly journals Crosstalk between Long-Term Sublethal Oxidative Stress and Detrimental Inflammation as Potential Drivers for Age-Related Retinal Degeneration

Antioxidants ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 25
Author(s):  
Lara Macchioni ◽  
Davide Chiasserini ◽  
Letizia Mezzasoma ◽  
Magdalena Davidescu ◽  
Pier Luigi Orvietani ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Age Related Macular Degeneration ◽  
Inflammasome Activation ◽  
Related Factor ◽  
Nuclear Factor ◽  
Rpe Cells ◽  
Age Related ◽  
Oxidative Insult

Age-related retinal degenerations, including age-related macular degeneration (AMD), are caused by the loss of retinal pigmented epithelial (RPE) cells and photoreceptors. The pathogenesis of AMD, deeply linked to the aging process, also involves oxidative stress and inflammatory responses. However, the molecular mechanisms contributing to the shift from healthy aging to AMD are still poorly understood. Since RPE cells in the retina are chronically exposed to a pro-oxidant microenvironment throughout life, we simulated in vivo conditions by growing ARPE-19 cells in the presence of 10 μM H2O2 for several passages. This long-term oxidative insult induced senescence in ARPE-19 cells without affecting cell proliferation. Global proteomic analysis revealed a dysregulated expression in proteins involved in antioxidant response, mitochondrial homeostasis, and extracellular matrix organization. The analyses of mitochondrial functionality showed increased mitochondrial biogenesis and ATP generation and improved response to oxidative stress. The latter, however, was linked to nuclear factor-κB (NF-κB) rather than nuclear factor erythroid 2–related factor 2 (Nrf2) activation. NF-κB hyperactivation also resulted in increased pro-inflammatory cytokines expression and inflammasome activation. Moreover, in response to additional pro-inflammatory insults, senescent ARPE-19 cells underwent an exaggerated inflammatory reaction. Our results indicate senescence as an important link between chronic oxidative insult and detrimental chronic inflammation, with possible future repercussions for therapeutic interventions.

scholarly journals Risk Factors of Metabolic Syndrome among Polish Nurses

Metabolites ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 267
Author(s):  
Anna Bartosiewicz ◽  
Edyta Łuszczki ◽  
Małgorzata Nagórska ◽  
Łukasz Oleksy ◽  
Artur Stolarczyk ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Weight Control ◽  
Professional Group ◽  
Overweight And Obesity ◽  
World Health ◽  
Dietary Recommendations ◽  
Obesity Class ◽  
The Metabolic Syndrome ◽  
The World

The metabolic syndrome, also known as syndrome X or the insulin resistance, is defined by the World Health Organization as a pathologic condition characterized by abdominal obesity, insulin resistance, hypertension, and hyperlipidemia. Both all over the world and in Poland, there is a shortage of nurses; most of those employed are in the pre-retirement age. However, the requirements in this profession and the patient’s right to care at the highest level remain unchanged and do not take into account the poor condition or age of working nurses, so special attention should be paid to the state of health in this professional group. There is an emphasis on the importance of the adopted attitude toward health and the resulting behaviors, such as regular weight control, following dietary recommendations, regular physical activity and participation in preventive examinations. The aim of the study was to assess the frequency of the occurrence of the metabolic syndrome, its individual components and determining the factors influencing its development in Polish nurses. The research conducted among the nurses in question included DXA (Dual Energy X-ray Absorptiometry) measurements, assessment of glucose concentration, lipid profile, blood pressure and a questionnaire survey. Almost half of the surveyed nurses have metabolic syndrome, which significantly increases the risk of developing cardiovascular diseases or diabetes. After multivariate analysis, it was found that being overweight and obesity were significant factors influenced the MS (metabolic syndrome) occurrence among Polish nurses. Being overweight increases the chances of MS occurrence 8.58 times in relation to BMI (Body Mass Index) <25, obesity increases the chances of MS occurrence 8.085 times in relation to BMI <25, and obesity class II/III increases the chances of MS occurrence 16.505 times in relation to BMI <25. Preventive and supportive measures for this professional group are needed.

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