Insulin resistance accounts for metabolic syndrome-related alterations in brain structure.
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ABSTRACT:
SUBMITTER: Lu R
PROVIDER: S-EPMC8090787 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: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.
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Project description:Obesity and its consequent complications such as hypertension and metabolic syndrome are increasing in incidence in almost all countries. Insulin resistance is common in obesity. Renin- angiotensin system (RAS) is an important target in the treatment of hypertension and drugs that act on RAS improve insulin resistance and decrease the incidence of type 2 diabetes mellitus, explaining the close association between hypertension and type 2 diabetes mellitus. RAS influences food intake by modulating the hypothalamic expression of neuropeptide Y and orexins via AMPK dephosphorylation. Estrogen reduces appetite by its action on the brain in a way similar to leptin, an anorexigenic action that seems to be mediated via hypothalamic pro-opiomelanocortin (POMC) neurons in the arcuate nucleus and synaptic plasticity in the arcuate nucleus similar to leptin. Estrogen stimulates lipoxin A4, a potent vasodilator and platelet anti-aggregator. Since both RAS and estrogen act on the hypothalamic neuropeptides and regulate food intake and obesity, it is likely that RAS modulates LXA4 synthesis. Thus, it is proposed that Angiotensin-II receptor blockers and angiotensin-converting enzymes and angiotensin-II antagonists may have the ability to augment LXA4 synthesis and thus bring about their beneficial actions.
| S-EPMC5290902 | biostudies-literature
Project description:UnlabelledAims/Introduction:? It is important to identify individuals at risk of metabolic syndrome (MetS), namely those with insulin resistance. Therefore, the aim of the present study was to find anthropometric and metabolic parameters that can better predict insulin resistance.Subjects and methods? We selected 3899 individuals (2058 men and 1841 women), excluding those with fasting plasma glucose (FPG) ?126?mg/dL, on medication for hypertension, dyslipidemia or diabetes, and those with a history of advanced macrovascular disease. Using multivariate analyses, we selected components for obesity, lipids, and blood pressure based on the strength of their association with the homeostasis model assessment of insulin resistance (HOMA-IR).Results? In multiple linear regression analysis, body mass index (BMI), waist circumference (WC), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C), and systolic blood pressure (SBP) were selected in men and women, and the effect of BMI on HOMA-IR outweighed that of WC. In multiple logistic regression analysis, BMI, TG, and SBP were significantly associated with HOMA-IR ?2.5 in both genders, but WC and HDL-C were only selected in men. Combinations of BMI, TG, SBP, and FPG showed higher HOMA-IR values than those of the existing MetS components, considered useful for the identification of individual with higher insulin resistance.Conclusions? Body mass index, TG and SBP were selected as components significantly related to insulin resistance. The selected components were fundamentally adherent to the existing MetS criteria, the only difference being the measure of obesity, in which a stronger association with insulin resistance was observed for BMI than WC. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00162.x, 2011).
| S-EPMC4020738 | biostudies-literature
Project description:Psoriasis in adults is associated with an increased risk of metabolic disease. Various cardiometabolic comorbidities have been reported in childhood psoriasis, but only a few studies have analyzed the prevalence of metabolic syndrome. We performed a single-center prospective study investigating the prevalence of metabolic syndrome and insulin resistance in children with psoriasis. The prevalence of metabolic syndrome was evaluated in 60 pre-pubertal children with psoriasis (age: 3-10 years), accordingly to recently established criteria for the diagnosis of metabolic syndrome in children. Insulin resistance was considered altered when the homeostatic model assessment (HOMA-IR) for insulin resistance was ≥ 90th sex- and age-specific percentile and HOMA 2-IR was > 1.8. Eighteen (30%) children with psoriasis were found to have metabolic syndrome. Sixteen (27%) children were found to have insulin resistance.Conclusion: Our data underline the importance of assessing metabolic syndrome not only in adults and adolescents but also in young children with psoriasis. What is Known: • Psoriasis in adults is strongly associated with metabolic disease and insulin resistance. • Very limited data are available on the prevalence of metabolic syndrome and insulin resistance in pre-pubertal children with psoriasis. What is New: • This study reports that in pre-pubertal children with psoriasis, there is a high prevalence of metabolic syndrome and insulin resistance. • In children with psoriasis metabolic syndrome risk factors should be assessed.
| S-EPMC8105196 | biostudies-literature
Project description:ObjectiveWe assessed the sex-specific differences in the molecular mechanisms of insulin resistance in muscle and adipose tissue, in a MS rat model induced by a high sucrose diet.MethodsMale, female, and ovariectomized female Wistar rats were randomly distributed in control and high-sucrose diet (HSD) groups, supplemented for 24 weeks with 20% sucrose in the drinking water. At the end, we assessed parameters related to MS, analyzing the effects of the HSD on critical nodes of the insulin signaling pathway in muscle and adipose tissue.ResultsAt the end of the treatment, HSD groups of both sexes developed obesity, with a 15, 33 and 23% of body weight gain in male, female, and OVX groups respectively, compared with controls; mainly related to hypertrophy of peripancreatic and gonadal adipose tissue. They also developed hypertriglyceridemia, and liver steatosis, with the last being worse in the HSD females. Compared to the control groups, HSD rats had higher IL1B and TNFA levels and insulin resistance. HSD females were more intolerant to glucose than HSD males. Our observations suggest that insulin resistance mechanisms include an increase in phosphorylated AKT(S473) form in HSD male and female groups and a decrease in phosphorylated P70S6K1(T389) in the HSD male groups from peripancreatic adipose tissue. While in gonadal adipose tissue the phosphorylated form of AKT decreased in HSD females, but not in HSD males. Finally, HSD groups showed a reduction in p-AKT levels in gastrocnemius muscle.ConclusionA high-sucrose diet induces MS and insulin resistance with sex-associated differences and in a tissue-specific manner.
| S-EPMC7583132 | biostudies-literature
Project description:This review summarizes the current understanding of the genetic basis of glucose homeostasis through genome-wide association scans and candidate gene studies of case-control and family-based designs. We highlight the implications of phenotype-direct (euglycemic clamp or frequently sampled intravenous glucose tolerance test) and indirect (fasting insulin and fasting glucose) measures on the determinants of insulin resistance and β-cell response that precede and contribute to the development of type 2 diabetes mellitus (T2DM) and the metabolic syndrome. Finally, we examine future approaches that may aid in understanding the biology of insulin resistance and T2DM. Over the past 2 decades, the prevalence of insulin resistance, the metabolic syndrome, and T2DM has increased. Ethnic differences in T2DM and insulin resistance are evident, with nonwhite populations having the greatest risk. There continue to be significant gaps in our knowledge regarding the metabolic, behavioral, and genetic determinants of these conditions. Understanding the genetic basis of glucose homeostasis, insulin resistance, and T2DM should provide insight on known and novel metabolic pathways that identify potential therapeutic targets and mechanisms for intervention.
| S-EPMC3988457 | biostudies-literature
Project description:BackgroundInsulin resistance is a frequent precursor of typical obesity and metabolic syndrome complications. However, accurate diagnosis remains elusive because of its pathophysiological complexity and heterogeneity. Herein, we have explored the utility of insulin secretion dynamics in response to an oral glucose tolerance test as a surrogate marker to identify distinct metabotypes of disease severity.MethodsThe study population consisted of children with obesity and insulin resistance, stratified according to the post-challenge insulin peak timing (i.e., early, middle, and late peak), from whom fasting and postprandial plasma and erythrocytes were collected for metabolomics analysis.ResultsChildren with late insulin peak manifested worse cardiometabolic health (i.e., higher blood pressure, glycemia, and HOMA-IR scores) than early responders. These subjects also showed more pronounced changes in metabolites mirroring failures in energy homeostasis, oxidative stress, metabolism of cholesterol and phospholipids, and adherence to unhealthy dietary habits. Furthermore, delayed insulin peak was associated with impaired metabolic flexibility, as reflected in compromised capacity to regulate mitochondrial energy pathways and the antioxidant defense in response to glucose overload.ConclusionsAltogether, these findings suggest that insulin resistance could encompass several phenotypic subtypes characterized by graded disturbances in distinctive metabolic derangements occurring in childhood obesity, which serve as severity predictive markers.
| S-EPMC11348533 | biostudies-literature
Project description:In view of the high incidence of metabolic syndrome and the role of exercise in promoting metabolic disorders, the present study aimed to investigate the therapeutic effects of swimming intervention on metabolic syndrome. In the present study, a total of 100 patients with metabolic syndrome and 100 healthy individuals were included. Fasting blood was extracted from each participant, and the serum levels of interleukin (IL)-1, high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor ? (TNF-?) and IL-8 were measured by sandwich enzyme-linked immunosorbent assay. Patients were randomly divided into five groups (groups A-E). Patients in group A was treated with conventional drug treatment. Besides conventional treatment, patients in groups B-E were also subjected to swimming intervention for 15, 30, 45 and 60 min each time, respectively, four times a week for 3 months. Changes in the homeostatic model assessment of ?-cell function and insulin resistance (HOMA-IR) score, and in the serum levels of IL-1, hs-CRP, TNF-? and IL-8 were recorded. Furthermore, muscle tissues were collected from patients, and the expression levels of insulin receptor substrate-1 (IRS-1), glucose transporter type 4 (GLUT4) and protein kinase B (Akt) in the tissues were detected by western blot assay. The results revealed that HOMA-IR and the serum levels of IL-1, hs-CRP, TNF-? and IL-8 were significantly higher in metabolic syndrome patients as compared with those in the normal controls, while swimming intervention reduced HOMA-IR and these serum levels to different extents. Swimming intervention also promoted IRS-1 and Akt phosphorylation, and increased GLUT4 expression level. Thus, it is concluded that swimming intervention may improve metabolic syndrome through multiple pathways.
| S-EPMC6307524 | biostudies-other
Project description:Obesity and its comorbidities, including type 2 diabetes mellitus and cardiovascular disease, are associated with a state of chronic low-grade inflammation that can be detected both systemically and within specific tissues. Areas of active investigation focus on the molecular bases of metabolic inflammation and potential pathogenic roles in insulin resistance, diabetes, and cardiovascular disease. An increased accumulation of macrophages occurring in obese adipose tissue has emerged as a key process in metabolic inflammation. Recent studies have also begun to unravel the heterogeneity of adipose tissue macrophages, and their physical and functional interactions with adipocytes, endothelial cells, and other immune cells within the adipose tissue microenvironment. Translating the information gathered from experimental models of insulin resistance and diabetes into meaningful therapeutic interventions is a tantalizing goal with long-term global health implications. In this context, ongoing clinical studies are testing the effects of targeting inflammation systemically on metabolic and cardiovascular outcomes.
| S-EPMC4784686 | biostudies-literature
Project description:Background and purposeMetabolic and cardiovascular abnormalities accompanying metabolic syndrome, such as obesity, insulin resistance and hypertension, are all associated with endothelial dysfunction and are independent risk factors for erectile dysfunction. The purpose of the present study was to investigate the vascular effects of insulin in penile arteries and whether these effects are impaired in a rat model of insulin resistance and metabolic syndrome.Experimental approachPenile arteries from obese Zucker rats (OZR) and their counterpart, lean Zucker rats (LZR), were mounted on microvascular myographs and the effects of insulin were assessed in the absence and presence of endothelium and of specific inhibitors of nitric oxide (NO) synthesis, phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK). Insulin-induced changes in intracellular Ca(2+) concentration [Ca(2+)](i) were also examined. KEY RESULTS OZR exhibited mild hyperglycaemia, hypercholesterolemia, hypertryglyceridemia and hyperinsulinemia. Insulin induced endothelium- and NO-dependent relaxations in LZR that were impaired in OZR. Inhibition of PI3K reduced relaxation induced by insulin and by the beta-adrenoceptor agonist isoprenaline, mainly in arteries from LZR. Antagonism of endothelin 1 (ET-1) receptors did not alter insulin-induced relaxation in either LZR or OZR, but MAPK blockade increased the responses in OZR. Insulin decreased [Ca(2+)](i), a response impaired in OZR.Conclusions and implicationsInsulin-induced relaxation was impaired in penile arteries of OZR due to altered NO release through the PI3K pathway and unmasking of a MAPK-mediated vasoconstriction. This vascular insulin resistance is likely to contribute to the endothelial dysfunction and erectile dysfunction associated with insulin resistant states.
| S-EPMC2989587 | biostudies-literature