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Diabetes & Metabolism Journal Jan 2022Insulin resistance is the pivotal pathogenic component of many metabolic diseases, including type 2 diabetes mellitus, and is defined as a state of reduced... (Review)
Review
Insulin resistance is the pivotal pathogenic component of many metabolic diseases, including type 2 diabetes mellitus, and is defined as a state of reduced responsiveness of insulin-targeting tissues to physiological levels of insulin. Although the underlying mechanism of insulin resistance is not fully understood, several credible theories have been proposed. In this review, we summarize the functions of insulin in glucose metabolism in typical metabolic tissues and describe the mechanisms proposed to underlie insulin resistance, that is, ectopic lipid accumulation in liver and skeletal muscle, endoplasmic reticulum stress, and inflammation. In addition, we suggest potential therapeutic strategies for addressing insulin resistance.
Topics: Diabetes Mellitus, Type 2; Endoplasmic Reticulum Stress; Humans; Insulin; Insulin Resistance; Muscle, Skeletal
PubMed: 34965646
DOI: 10.4093/dmj.2021.0280 -
International Journal of Molecular... Jan 2022Metabolic syndrome (MetS) forms a cluster of metabolic dysregulations including insulin resistance, atherogenic dyslipidemia, central obesity, and hypertension. The... (Review)
Review
Metabolic syndrome (MetS) forms a cluster of metabolic dysregulations including insulin resistance, atherogenic dyslipidemia, central obesity, and hypertension. The pathogenesis of MetS encompasses multiple genetic and acquired entities that fall under the umbrella of insulin resistance and chronic low-grade inflammation. If left untreated, MetS is significantly associated with an increased risk of developing diabetes and cardiovascular diseases (CVDs). Given that CVDs constitute by far the leading cause of morbidity and mortality worldwide, it has become essential to investigate the role played by MetS in this context to reduce the heavy burden of the disease. As such, and while MetS relatively constitutes a novel clinical entity, the extent of research about the disease has been exponentially growing in the past few decades. However, many aspects of this clinical entity are still not completely understood, and many questions remain unanswered to date. In this review, we provide a historical background and highlight the epidemiology of MetS. We also discuss the current and latest knowledge about the histopathology and pathophysiology of the disease. Finally, we summarize the most recent updates about the management and the prevention of this clinical syndrome.
Topics: Biomarkers; Chronic Disease; Disease Management; Disease Susceptibility; Humans; Inflammation; Insulin Resistance; Metabolic Syndrome; Mitochondria; Organ Specificity; Prevalence; Public Health Surveillance
PubMed: 35054972
DOI: 10.3390/ijms23020786 -
Current Hypertension Reports Feb 2018Metabolic syndrome, variously known also as syndrome X, insulin resistance, etc., is defined by WHO as a pathologic condition characterized by abdominal obesity, insulin... (Review)
Review
Metabolic syndrome, variously known also as syndrome X, insulin resistance, etc., is defined by WHO as a pathologic condition characterized by abdominal obesity, insulin resistance, hypertension, and hyperlipidemia. Though there is some variation in the definition by other health care organization, the differences are minor. With the successful conquest of communicable infectious diseases in most of the world, this new non-communicable disease (NCD) has become the major health hazard of modern world. Though it started in the Western world, with the spread of the Western lifestyle across the globe, it has become now a truly global problem. The prevalence of the metabolic syndrome is often more in the urban population of some developing countries than in its Western counterparts. The two basic forces spreading this malady are the increase in consumption of high calorie-low fiber fast food and the decrease in physical activity due to mechanized transportations and sedentary form of leisure time activities. The syndrome feeds into the spread of the diseases like type 2 diabetes, coronary diseases, stroke, and other disabilities. The total cost of the malady including the cost of health care and loss of potential economic activity is in trillions. The present trend is not sustainable unless a magic cure is found (unlikely) or concerted global/governmental/societal efforts are made to change the lifestyle that is promoting it. There are certainly some elements in the causation of the metabolic syndrome that cannot be changed but many are amenable for corrections and curtailments. For example, better urban planning to encourage active lifestyle, subsidizing consumption of whole grains and possible taxing high calorie snacks, restricting media advertisement of unhealthy food, etc. Revitalizing old fashion healthier lifestyle, promoting old-fashioned foods using healthy herbs rather than oil and sugar, and educating people about choosing healthy/wholesome food over junks are among the steps that can be considered.
Topics: Epidemics; Exercise; Female; Global Health; Humans; Incidence; Life Style; Male; Metabolic Syndrome; Prevalence
PubMed: 29480368
DOI: 10.1007/s11906-018-0812-z -
Comprehensive Physiology Jan 2013Metabolic syndrome (MS) is a collection of cardiometabolic risk factors that includes obesity, insulin resistance, hypertension, and dyslipidemia. Although there has... (Review)
Review
Metabolic syndrome (MS) is a collection of cardiometabolic risk factors that includes obesity, insulin resistance, hypertension, and dyslipidemia. Although there has been significant debate regarding the criteria and concept of the syndrome, this clustering of risk factors is unequivocally linked to an increased risk of developing type 2 diabetes and cardiovascular disease. Regardless of the true definition, based on current population estimates, nearly 100 million have MS. It is often characterized by insulin resistance, which some have suggested is a major underpinning link between physical inactivity and MS. The purpose of this review is to: (i) provide an overview of the history, causes and clinical aspects of MS, (ii) review the molecular mechanisms of insulin action and the causes of insulin resistance, and (iii) discuss the epidemiological and intervention data on the effects of exercise on MS and insulin sensitivity.
Topics: Animals; Exercise Therapy; Humans; Insulin; Insulin Resistance; Metabolic Syndrome; Motor Activity; Receptor, Insulin
PubMed: 23720280
DOI: 10.1002/cphy.c110062 -
Canadian Journal of Gastroenterology &... 2021Nonalcoholic fatty liver disease is a condition defined by fat accumulation in hepatocytes not promoted by excessive alcohol consumption. It is highly prevalent and is... (Review)
Review
Nonalcoholic fatty liver disease is a condition defined by fat accumulation in hepatocytes not promoted by excessive alcohol consumption. It is highly prevalent and is strongly associated with insulin resistance, metabolic syndrome, and diabetes type II. Insulin resistance plays a crucial role in the multifactorial etiopathogenesis of this condition leading to accumulation of free fatty acids in the liver cells, thus causing lipotoxicity, inflammation, and fibrosis. In this review, we will focus on currently known pathogenesis of nonalcoholic fatty liver disease. Numerous investigation strategies are available to establish the diagnosis, from biochemical markers and ultrasound to various molecular and advanced imaging techniques and liver biopsy. Prevention is crucial. However, effective and promising therapies are strongly demanded.
Topics: Diabetes Mellitus, Type 2; Hepatocytes; Humans; Insulin Resistance; Liver; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease
PubMed: 33681089
DOI: 10.1155/2021/6613827 -
The Journal of International Medical... Mar 2023Insulin resistance (IR) and cardiovascular disease (CVD) represent two universal public health hazards, especially in today's Western societies. A causal-effect... (Review)
Review
Insulin resistance (IR) and cardiovascular disease (CVD) represent two universal public health hazards, especially in today's Western societies. A causal-effect relationship has been established that links IR with CVD. The mediating mechanisms are perplexing, under ongoing, rigorous investigation and remain to be fully elucidated. IR is a condition encompassing hyperglycemia and compensatory hyperinsulinemia. It occurs when insulin is not capable of exerting its maximum effects on target tissues, including skeletal muscles, liver and adipose tissue. This alteration of insulin signaling pathways results in the development of cardiometabolic disorders, including obesity, dyslipidemia, low-grade inflammation, endothelial dysfunction and hypertension, all of which are predisposing factors for atherosclerosis and CVD. The management of IR can be achieved through dietary modifications, the inclusion of regular exercise routines in everyday life, pharmacological agents and other interventions tailored to each individual patient's needs. It is important to underline though that, although various antidiabetic drugs that may improve IR are available, no medications are as yet specifically approved for the treatment of IR. This narrative review will focus on the current scientific and clinical evidence pertaining to IR, the mechanisms connecting IR with CVD, as well as plausible strategies for a holistic, personalized approach for IR management.
Topics: Humans; Insulin Resistance; Cardiovascular Diseases; Obesity; Hypertension; Insulin
PubMed: 36994866
DOI: 10.1177/03000605231164548 -
Current Cardiology Reports Aug 2016Insulin resistance and the metabolic syndrome are complex metabolic traits and key risk factors for the development of cardiovascular disease. They result from the... (Review)
Review
Insulin resistance and the metabolic syndrome are complex metabolic traits and key risk factors for the development of cardiovascular disease. They result from the interplay of environmental and genetic factors but the full extent of the genetic background to these conditions remains incomplete. Large-scale genome-wide association studies have helped advance the identification of common genetic variation associated with insulin resistance and the metabolic syndrome, and more recently, exome sequencing has allowed the identification of rare variants associated with the pathogenesis of these conditions. Many variants associated with insulin resistance are directly involved in glucose metabolism; however, functional studies are required to assess the contribution of other variants to the development of insulin resistance. Many genetic variants involved in the pathogenesis of the metabolic syndrome are associated with lipid metabolism.
Topics: Diabetes Mellitus, Type 2; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Insulin Resistance; Lipid Metabolism; Metabolic Syndrome; Polymorphism, Single Nucleotide
PubMed: 27312935
DOI: 10.1007/s11886-016-0755-4 -
Nutrients Jul 2019Both observational and interventional studies suggest an important role for physical activity and higher fitness in mitigating the metabolic syndrome. Each component of... (Review)
Review
Both observational and interventional studies suggest an important role for physical activity and higher fitness in mitigating the metabolic syndrome. Each component of the metabolic syndrome is, to a certain extent, favorably influenced by interventions that include physical activity. Given that the prevalence of the metabolic syndrome and its individual components (particularly obesity and insulin resistance) has increased significantly in recent decades, guidelines from various professional organizations have called for greater efforts to reduce the incidence of this condition and its components. While physical activity interventions that lead to improved fitness cannot be expected to normalize insulin resistance, lipid disorders, or obesity, the combined effect of increasing activity on these risk markers, an improvement in fitness, or both, has been shown to have a major impact on health outcomes related to the metabolic syndrome. Exercise therapy is a cost-effective intervention to both prevent and mitigate the impact of the metabolic syndrome, but it remains underutilized. In the current article, an overview of the effects of physical activity and higher fitness on the metabolic syndrome is provided, along with a discussion of the mechanisms underlying the benefits of being more fit or more physically active in the prevention and treatment of the metabolic syndrome.
Topics: Adult; Cardiorespiratory Fitness; Cardiovascular Diseases; Exercise; Female; Humans; Insulin Resistance; Male; Metabolic Syndrome; Middle Aged; Obesity; Physical Fitness; Risk Factors
PubMed: 31331009
DOI: 10.3390/nu11071652 -
Nature Reviews. Molecular Cell Biology Oct 2018The cause of insulin resistance in obesity and type 2 diabetes mellitus (T2DM) is not limited to impaired insulin signalling but also involves the complex interplay of... (Review)
Review
The cause of insulin resistance in obesity and type 2 diabetes mellitus (T2DM) is not limited to impaired insulin signalling but also involves the complex interplay of multiple metabolic pathways. The analysis of large data sets generated by metabolomics and lipidomics has shed new light on the roles of metabolites such as lipids, amino acids and bile acids in modulating insulin sensitivity. Metabolites can regulate insulin sensitivity directly by modulating components of the insulin signalling pathway, such as insulin receptor substrates (IRSs) and AKT, and indirectly by altering the flux of substrates through multiple metabolic pathways, including lipogenesis, lipid oxidation, protein synthesis and degradation and hepatic gluconeogenesis. Moreover, the post-translational modification of proteins by metabolites and lipids, including acetylation and palmitoylation, can alter protein function. Furthermore, the role of the microbiota in regulating substrate metabolism and insulin sensitivity is unfolding. In this Review, we discuss the emerging roles of metabolites in the pathogenesis of insulin resistance and T2DM. A comprehensive understanding of the metabolic adaptations involved in insulin resistance may enable the identification of novel targets for improving insulin sensitivity and preventing, and treating, T2DM.
Topics: Animals; Diabetes Mellitus, Type 2; Glucose; Glucose Metabolism Disorders; Humans; Insulin; Insulin Resistance; Lipid Metabolism; Liver; Metabolic Networks and Pathways; Metabolomics; Obesity; Receptor, Insulin; Signal Transduction
PubMed: 30104701
DOI: 10.1038/s41580-018-0044-8 -
Eating and Weight Disorders : EWD Apr 2018Obesity is a major health risk factor, and obesity-induced morbidity and complications account for huge costs for affected individuals, families, healthcare systems, and... (Review)
Review
Obesity is a major health risk factor, and obesity-induced morbidity and complications account for huge costs for affected individuals, families, healthcare systems, and society at large. In particular, obesity is strongly associated with the development of insulin resistance, which in turn plays a key role in the pathogenesis of obesity-associated cardiometabolic complications, including metabolic syndrome components, type 2 diabetes, and cardiovascular diseases. Insulin sensitive tissues, including adipose tissue, skeletal muscle, and liver, are profoundly affected by obesity both at biomolecular and functional levels. Altered adipose organ function may play a fundamental pathogenetic role once fat accumulation has ensued. Modulation of insulin sensitivity appears to be, at least in part, related to changes in redox balance and oxidative stress as well as inflammation, with a relevant underlying role for mitochondrial dysfunction that may exacerbate these alterations. Nutrients and substrates as well as systems involved in host-nutrient interactions, including gut microbiota, have been also identified as modulators of metabolic pathways controlling insulin action. This review aims at providing an overview of these concepts and their potential inter-relationships in the development of insulin resistance, with particular regard to changes in adipose organ and skeletal muscle.
Topics: Diabetes Mellitus, Type 2; Humans; Inflammation; Insulin Resistance; Obesity; Oxidative Stress
PubMed: 29397563
DOI: 10.1007/s40519-018-0481-6