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.

scholarly journals Emerging roles of C1Q tumor necrosis factor-related proteins in metabolic diseases

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Manjunath Ramanjaneya ◽  
Jayakumar Jerobin ◽  
Ilham Bettahi ◽  
Kodappully Sivaraman Siveen ◽  
Abdul-Badi Abou-Samra
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Metabolic Disorders ◽  
Pharmacological Intervention ◽  
Alcoholic Fatty Liver ◽  
The Metabolic Syndrome ◽  
Related Proteins ◽  
Necrosis Factor

AbstractObesity and insulin resistance are key elements of the metabolic syndrome, which includes type 2 diabetes (T2D), dyslipidemia, systemic inflammation, hypertension, elevated risk for cardiovascular diseases, non-alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS). C1Q Tumor necrosis factor-related proteins (CTRPs) have recently emerged as important regulators of metabolism as a core component in the interrelationship between insulin resistance, adiposity and inflammation. To date 15 CTRP members have been identified and most of the CTRPs are dysregulated in obesity, T2D, coronary artery disease and NAFLD. Pharmacological intervention and lifestyle modification alter expression of CTRPs in circulation and in metabolically active tissues. CTRPs enhance metabolism mainly through activation of AMPK/AKT dependent pathways and possess insulin sensitizing properties. Thus dysregulated expression of CTRPs in metabolic disorders could contribute to the pathogenesis of the disease. For these reasons CTRPs appear to be promising targets for early detection, prevention and treatment of metabolic disorders. This review article aims at exploring the role of CTRPs in metabolic syndrome.

scholarly journals Exercise Induced Adipokine Changes and the Metabolic Syndrome

2014 ◽  
Vol 2014 ◽  
pp. 1-16 ◽  
Author(s):  
Saeid Golbidi ◽  
Ismail Laher
Keyword(s):  
Physical Activity ◽  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
The Body ◽  
Beneficial Effects ◽  
The Metabolic Syndrome ◽  
Before And After ◽  
Inflammatory State ◽  
Exercise Induced

The lack of adequate physical activity and obesity created a worldwide pandemic. Obesity is characterized by the deposition of adipose tissue in various parts of the body; it is now evident that adipose tissue also acts as an endocrine organ capable of secreting many cytokines that are though to be involved in the pathophysiology of obesity, insulin resistance, and metabolic syndrome. Adipokines, or adipose tissue-derived proteins, play a pivotal role in this scenario. Increased secretion of proinflammatory adipokines leads to a chronic inflammatory state that is accompanied by insulin resistance and glucose intolerance. Lifestyle change in terms of increased physical activity and exercise is the best nonpharmacological treatment for obesity since these can reduce insulin resistance, counteract the inflammatory state, and improve the lipid profile. There is growing evidence that exercise exerts its beneficial effects partly through alterations in the adipokine profile; that is, exercise increases secretion of anti-inflammatory adipokines and reduces proinflammatory cytokines. In this paper we briefly describe the pathophysiologic role of four important adipokines (adiponectin, leptin, TNF-α, and IL-6) in the metabolic syndrome and review some of the clinical trials that monitored these adipokines as a clinical outcome before and after exercise.

Modulation of the action of insulin by angiotensin-(1–7)

2014 ◽  
Vol 126 (9) ◽  
pp. 613-630 ◽  
Author(s):  
Fernando P. Dominici ◽  
Valeria Burghi ◽  
Marina C. Muñoz ◽  
Jorge F. Giani
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Molecular Mechanisms ◽  
Insulin Signalling ◽  
Pathological Condition ◽  
Signalling Pathway ◽  
Systemic Hypertension ◽  
The Metabolic Syndrome ◽  
Insulin Signalling Pathway ◽  
Cardiovascular Morbidity And Mortality

The prevalence of Type 2 diabetes mellitus is predicted to increase dramatically over the coming years and the clinical implications and healthcare costs from this disease are overwhelming. In many cases, this pathological condition is linked to a cluster of metabolic disorders, such as obesity, systemic hypertension and dyslipidaemia, defined as the metabolic syndrome. Insulin resistance has been proposed as the key mediator of all of these features and contributes to the associated high cardiovascular morbidity and mortality. Although the molecular mechanisms behind insulin resistance are not completely understood, a negative cross-talk between AngII (angiotensin II) and the insulin signalling pathway has been the focus of great interest in the last decade. Indeed, substantial evidence has shown that anti-hypertensive drugs that block the RAS (renin–angiotensin system) may also act to prevent diabetes. Despite its long history, new components within the RAS continue to be discovered. Among them, Ang-(1–7) [angiotensin-(1–7)] has gained special attention as a counter-regulatory hormone opposing many of the AngII-related deleterious effects. Specifically, we and others have demonstrated that Ang-(1–7) improves the action of insulin and opposes the negative effect that AngII exerts at this level. In the present review, we provide evidence showing that insulin and Ang-(1–7) share a common intracellular signalling pathway. We also address the molecular mechanisms behind the beneficial effects of Ang-(1–7) on AngII-mediated insulin resistance. Finally, we discuss potential therapeutic approaches leading to modulation of the ACE2 (angiotensin-converting enzyme 2)/Ang-(1–7)/Mas receptor axis as a very attractive strategy in the therapy of the metabolic syndrome and diabetes-associated diseases.

scholarly journals Homeostasis of Glucose and Lipid in Non-Alcoholic Fatty Liver Disease

2019 ◽  
Vol 20 (2) ◽  
pp. 298 ◽  
Author(s):  
Hsu-Wen Chao ◽  
Shi-Wei Chao ◽  
Heng Lin ◽  
Hui-Chen Ku ◽  
Ching-Feng Cheng
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Liver Disease ◽  
Dietary Intake ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
The Metabolic Syndrome ◽  
Underlying Causes ◽  
Alcoholic Fatty Liver Disease

Industrialized society-caused dysregular human behaviors and activities such as overworking, excessive dietary intake, and sleep deprivation lead to perturbations in the metabolism and the development of metabolic syndrome. Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease worldwide, affects around 30% and 25% of people in Western and Asian countries, respectively, which leads to numerous medical costs annually. Insulin resistance is the major hallmark of NAFLD and is crucial in the pathogenesis and for the progression from NAFLD to non-alcoholic steatohepatitis (NASH). Excessive dietary intake of saturated fats and carbohydrate-enriched foods contributes to both insulin resistance and NAFLD. Once NAFLD is established, insulin resistance can promote the progression to the more severe state of liver endangerment like NASH. Here, we review current and potential studies for understanding the complexity between insulin-regulated glycolytic and lipogenic homeostasis and the underlying causes of NAFLD. We discuss how disruption of the insulin signal is associated with various metabolic disorders of glucoses and lipids that constitute both the metabolic syndrome and NAFLD.

scholarly journals Insulin resistance and insulin hypersecretion in the metabolic syndrome and type 2 diabetes: Time for a conceptual framework shift

2019 ◽  
Vol 16 (2) ◽  
pp. 118-127 ◽  
Author(s):  
Christopher J Nolan ◽  
Marc Prentki
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Conceptual Framework ◽  
Metabolic Health ◽  
Alternative View ◽  
Alcoholic Fatty Liver ◽  
The Metabolic Syndrome ◽  
Associated Conditions

While few dispute the existence of the metabolic syndrome as a clustering of factors indicative of poor metabolic health, its utility above that of its individual components in the clinical care of individual patients is questioned. This is likely a consequence of the failure of clinicians and scientists to agree on a unifying mechanism to explain the metabolic syndrome. Insulin resistance has most commonly been proposed for this role and is generally considered to be a root causative factor for not only metabolic syndrome but also for its associated conditions of non-alcoholic fatty liver disease (NAFLD), polycystic ovary syndrome (PCOS), obesity-related type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD). An alternative view, for which evidence is mounting, is that hyper-responsiveness of islet β-cells to a hostile environment, such as westernised lifestyle, is primary and that the resulting hyperinsulinaemia drives the other components of the metabolic syndrome. Importantly, within this new conceptual framework, insulin resistance, while always a biomarker and state of poor metabolic health, is not considered to be harmful, but a protective adaptive response of critical tissues including the myocardium against insulin-induced metabolic stress. This major shift in how metabolic syndrome can be considered puts insulin hypersecretion into position as the unifying mechanism. If shown to be correct, this new conceptual framework has major implications for the future prevention and management of the metabolic syndrome, including its associated conditions of NAFLD, PCOS, obesity-related T2D and ASCVD.

scholarly journals Luteolin-Enriched Artichoke Leaf Extract Alleviates the Metabolic Syndrome in Mice with High-Fat Diet-Induced Obesity

Nutrients ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 979 ◽  
Author(s):  
Eun-Young Kwon ◽  
So Kim ◽  
Myung-Sook Choi
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Acid Oxidation ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Diet Induced Obesity ◽  
The Metabolic Syndrome

This current study aimed to elucidate the effects and possible underlying mechanisms of long-term supplementation with dietary luteolin (LU)-enriched artichoke leaf (AR) in high-fat diet (HFD)-induced obesity and its complications (e.g., dyslipidemia, insulin resistance, and non-alcoholic fatty liver disease) in C57BL/6N mice. The mice were fed a normal diet, an HFD, or an HFD plus AR or LU for 16 weeks. In the HFD-fed mice, AR decreased the adiposity and dyslipidemia by decreasing lipogenesis while increasing fatty acid oxidation, which contributed to better hepatic steatosis. LU also prevented adiposity and hepatic steatosis by suppressing lipogenesis while increasing biliary sterol excretion. Moreover, AR and LU prevented insulin sensitivity by decreasing the level of plasma gastric inhibitory polypeptide and activity of hepatic glucogenic enzymes, which may be linked to the lowering of inflammation as evidenced by the reduced plasma interleukin (IL)-6, IL-1β, and plasminogen activator inhibitor-1 levels. Although the anti-metabolic syndrome effects of AR and LU were similar, the anti-adiposity and anti-dyslipidemic effects of AR were more pronounced. These results in mice with diet-induced obesity suggest that long-term supplementation with AR can prevent adiposity and related metabolic disorders such as dyslipidemia, hepatic steatosis, insulin resistance, and inflammation.

Molecular mechanisms for myocardial mitochondrial dysfunction in the metabolic syndrome

2008 ◽  
Vol 114 (3) ◽  
pp. 195-210 ◽  
Author(s):  
Heiko Bugger ◽  
E. Dale Abel
Keyword(s):  
Heart Failure ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Coronary Artery Disease ◽  
Metabolic Syndrome ◽  
Molecular Mechanisms ◽  
Contractile Dysfunction ◽  
The Metabolic Syndrome ◽  
Artery Disease

The metabolic syndrome represents a cluster of abnormalities, including obesity, insulin resistance, dyslipidaemia and Type 2 diabetes, that increases the risk of developing cardiovascular diseases, such as coronary artery disease and heart failure. The heart failure risk is increased even after adjusting for coronary artery disease and hypertension, and evidence is emerging that changes in cardiac energy metabolism might contribute to the development of contractile dysfunction. Recent findings suggest that myocardial mitochondrial dysfunction may play an important role in the pathogenesis of cardiac contractile dysfunction in obesity, insulin resistance and Type 2 diabetes. This review will discuss potential molecular mechanisms for these mitochondrial abnormalities.

scholarly journals Natriuretic peptides and cardiovascular damage in the metabolic syndrome: molecular mechanisms and clinical implications

2009 ◽  
Vol 118 (4) ◽  
pp. 231-240 ◽  
Author(s):  
Carmine Savoia ◽  
Massimo Volpe ◽  
Alessandro Alonzo ◽  
Chiara Rossi ◽  
Speranza Rubattu
Keyword(s):  
Insulin Resistance ◽  
Cardiovascular Disease ◽  
Metabolic Syndrome ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Molecular Mechanisms ◽  
Vascular Inflammation ◽  
Visceral Obesity ◽  
Blood Pressure Elevation ◽  
The Metabolic Syndrome

Natriuretic peptides are endogenous antagonists of vasoconstrictor and salt- and water-retaining systems in the body's defence against blood pressure elevation and plasma volume expansion, through direct vasodilator, diuretic and natriuretic properties. In addition, natriuretic peptides may play a role in the modulation of the molecular mechanisms involved in metabolic regulation and cardiovascular remodelling. The metabolic syndrome is characterized by visceral obesity, hyperlipidaemia, vascular inflammation and hypertension, which are linked by peripheral insulin resistance. Increased visceral adiposity may contribute to the reduction in the circulating levels of natriuretic peptides. The dysregulation of neurohormonal systems, including the renin–angiotensin and the natriuretic peptide systems, may in turn contribute to the development of insulin resistance in dysmetabolic patients. In obese subjects with the metabolic syndrome, reduced levels of natriuretic peptides may be involved in the development of hypertension, vascular inflammation and cardio vascular remodelling, and this may predispose to the development of cardiovascular disease. The present review summarizes the regulation and function of the natriuretic peptide system in obese patients with the metabolic syndrome and the involvement of altered bioactive levels of natriuretic peptides in the pathophysiology of cardiovascular disease in patients with metabolic abnormalities.

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