Trends in insulin resistance: insights into mechanisms and therapeutic strategy

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: July 6, 2022

The centenary of insulin discovery represents an important opportunity to transform diabetes from a fatal diagnosis into medically manageable chronic condition. Insulin is key peptide hormone and mediates the systemic glucose metabolism in different tissues. resistance (IR) disordered biological response for stimulation through disruption molecular pathways target Acquired conditions genetic factors have been implicated IR. Recent biochemical studies suggest that dysregulated metabolic mediators released by adipose tissue including adipokines, cytokines, chemokines, excess lipids toxic lipid metabolites promote IR other associated with several groups abnormal syndromes include obesity, diabetes, dysfunction-associated fatty liver disease (MAFLD), cardiovascular disease, polycystic ovary syndrome (PCOS), abnormalities. Although no medication specifically approved treat IR, we summarized lifestyle changes pharmacological medications used as efficient intervention improve sensitivity. Ultimately, systematic discussion complex mechanism will help identify potential new targets closely

Language: Английский

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Silymarin as Supportive Treatment in Liver Diseases: A Narrative Review

Advances in Therapy, Journal Year: 2020, Volume and Issue: 37(4), P. 1279 - 1301

Published: Feb. 17, 2020

Silymarin, an extract from milk thistle seeds, has been used for centuries to treat hepatic conditions. Preclinical data indicate that silymarin can reduce oxidative stress and consequent cytotoxicity, thereby protecting intact liver cells or not yet irreversibly damaged. Eurosil 85® is a proprietary formulation developed maximize the oral bioavailability of silymarin. Most clinical research on this formulation. Silymarin acts as free radical scavenger modulates enzymes associated with development cellular damage, fibrosis cirrhosis. These hepatoprotective effects were observed in studies patients alcoholic non-alcoholic fatty disease, including In pooled analysis trials cirrhosis, treatment was significant reduction liver-related deaths. Moreover, diabetes also able improve glycemic parameters. Patients drug-induced injuries successfully treated generally very well tolerated, low incidence adverse events no treatment-related serious deaths reported trials. For maximum benefit, should be initiated early possible disease other distinct manifestations such acute failure, when regenerative potential still high removal stress, cause achieve best results.

Language: Английский

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The Role of Insulin Resistance and Diabetes in Nonalcoholic Fatty Liver Disease

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(11), P. 3863 - 3863

Published: May 29, 2020

Nonalcoholic fatty liver disease (NAFLD) consists of the entire spectrum in patients without significant alcohol consumption, ranging from nonalcoholic (NAFL) to steatohepatitis (NASH) cirrhosis, with NASH recently shown as an important cause hepatocellular carcinoma (HCC). There is a close relationship between insulin resistance (IR) and NAFLD, five-fold higher prevalence NAFLD type 2 diabetes (T2DM) compared that T2DM. IR involved progression conditions such steatosis NASH, well hepatic fibrosis progression. The mechanisms underlying these processes involve genetic factors, fat accumulation, alterations energy metabolism, inflammatory signals derived various cell types including immune cells. In NASH-associated fibrosis, principal responsible for extracellular matrix production stellate (HSC). HSC activation by involves "direct" "indirect" pathways. This review will describe molecular inflammation IR, T2DM HCC NAFLD.

Language: Английский

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Quercetin improves nonalcoholic fatty liver by ameliorating inflammation, oxidative stress, and lipid metabolism in db/db mice

Phytotherapy Research, Journal Year: 2019, Volume and Issue: 33(12), P. 3140 - 3152

Published: Aug. 26, 2019

Multiphase pathological processes involve in Type 2 diabetes (T2DM)‐induced nonalcoholic fatty liver disease (NAFLD). However, the therapies are quite limited. In present study, hepatoprotective effects and underlying mechanisms of quercetin T2DM‐induced NAFLD were investigated. treatment models established vivo vitro. The results revealed that alleviated serum transaminase levels markedly reduced histological alterations livers. Additionally, restored superoxide dismutase, catalase, glutathione content Not only that, attenuated production interleukin 1 beta, 6, TNF‐α. Accompanied by restoration increased total bile acid ( p = .0001) decreased .0005), could reduce lipid accumulation db / mice. Further mechanism studies showed farnesoid X receptor 1/Takeda G‐protein‐coupled 5 signaling pathways was involved regulation metabolism NAFLD. high D‐glucose free cocultured HepG2 cells model, eliminated droplets upregulated cholesterol triglyceride levels. Similar to findings mice, also activate pathway. These suggested might be a potentially effective drug for

Language: Английский

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Non-alcoholic fatty liver disease, insulin resistance, metabolic syndrome and their association with vascular risk

Metabolism, Journal Year: 2021, Volume and Issue: 119, P. 154770 - 154770

Published: April 15, 2021

Language: Английский

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Nonalcoholic fatty liver disease as a metabolic disease in humans: A literature review

Diabetes Obesity and Metabolism, Journal Year: 2021, Volume and Issue: 23(5), P. 1069 - 1083

Published: Jan. 19, 2021

Abstract Aims To conduct a systematic literature review to identify recent epidemiological, biomarker, genetic and clinical evidence that expands our understanding of nonalcoholic fatty liver disease (NAFLD) as metabolic disorder. Materials Methods We performed search using PubMed trials, observational studies meta‐analyses published in the past 5 years. Results A total 95 publications met prespecified inclusion criteria reported on interplay between NAFLD/nonalcoholic steatohepatitis (NASH) dysfunction, terms burden and/or epidemiology (n = 10), pathophysiology, risk factors associated conditions 29), diagnosis biomarkers 34), treatment approaches 22). There is growing body links NAFLD/NASH pathogenesis mechanisms through lipid accumulation, insulin resistance, inflammation, apoptosis, fibrogenic remodelling within liver. The frequent co‐occurrence NAFLD with obesity, syndrome type 2 diabetes supports this premise. Therapeutic originally envisaged for or obesity (such glucagon‐like peptide‐1 receptor agonists, sodium‐glucose co‐transporter‐2 inhibitors, sensitizers bariatric surgery) have shown promising signs benefit patients NAFLD/NASH. Conclusions Given complex there an urgent need multidisciplinary collaboration established protocols care are individualized ideally support reduction overall well NASH.

Language: Английский

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Insulin Resistance and Diabetes Mellitus in Alzheimer’s Disease

Cells, Journal Year: 2021, Volume and Issue: 10(5), P. 1236 - 1236

Published: May 18, 2021

Type 2 diabetes mellitus is a progressive disease that characterized by the appearance of insulin resistance. The term resistance very wide and could affect different proteins involved in signaling, as well other mechanisms. In this review, we have analyzed main molecular mechanisms be connection between type neurodegeneration, general, more specifically with Alzheimer’s disease. We studied, detail, processes involved, such inflammation, endoplasmic reticulum stress, autophagy, mitochondrial dysfunction.

Language: Английский

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Atherosclerosis and Inflammation: Insights from the Theory of General Pathological Processes

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(9), P. 7910 - 7910

Published: April 26, 2023

Recent advances have greatly improved our understanding of the molecular mechanisms behind atherosclerosis pathogenesis. However, there is still a need to systematize this data from general pathology perspective, particularly with regard atherogenesis patterns in context both canonical and non-classical inflammation types. In review, we analyze various typical phenomena outcomes cellular pro-inflammatory stress atherosclerosis, as well role endothelial dysfunction local systemic manifestations low-grade inflammation. We also present features immune development productive stable unstable plaques, along their similarities differences compared There are numerous factors that act inducers inflammatory process including vascular endothelium aging, metabolic dysfunctions, autoimmune, some cases, infectious damage factors. Life-critical complications such cardiogenic shock severe strokes, associated acute hyperinflammation. Additionally, critical atherosclerotic ischemia lower extremities induces paracoagulation chronic Conversely, sepsis, other conditions, diseases contribute atherogenesis. summary, can be characterized an independent form inflammation, sharing but having fundamental variants (classic vasculitis).

Language: Английский

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Silymarin: Unveiling its pharmacological spectrum and therapeutic potential in liver diseases—A comprehensive narrative review

Food Science & Nutrition, Journal Year: 2024, Volume and Issue: 12(5), P. 3097 - 3111

Published: Feb. 16, 2024

Abstract Liver diseases, encompassing conditions such as cirrhosis, present a substantial global health challenge with diverse etiologies, including viral infections, alcohol consumption, and non‐alcoholic fatty liver disease (NAFLD). The exploration of natural compounds therapeutic agents has gained traction, notably the herbal remedy milk thistle ( Silybum marianum ), its active extract, silymarin, demonstrating remarkable antioxidant hepatoprotective properties in extensive preclinical investigations. It can protect healthy cells or those that have not yet sustained permanent damage by reducing oxidative stress mitigating cytotoxicity. Silymarin, compound properties, anti‐inflammatory effects, antifibrotic activity, shown potential treating caused alcohol, NAFLD, drug‐induced toxicity, hepatitis. Legalon® is top‐rated medication excellent oral bioavailability, effective absorption, effectiveness. Its component, Eurosil 85® also, commercial product, lipophilic enhanced special formulation processes. during clinical trials, shows improvements function, reduced mortality rates, alleviation symptoms across various disorders, safety assessments showing low adverse effects. Overall, silymarin emerges promising multifaceted diseases.

Language: Английский

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Association between the triglyceride-glucose index and liver fibrosis in adults with metabolism-related fatty liver disease in the United States: a cross-sectional study of NHANES 2017–2020

BMC Gastroenterology, Journal Year: 2025, Volume and Issue: 25(1)

Published: Jan. 2, 2025

This study aimed to examine the association between triglyceride-glucose (TyG) index and liver fibrosis (LF) in U.S. adults with Metabolic Dysfunction-Associated Steatotic Liver Disease (MAFLD). Using data from 2017 2020 National Health Nutrition Examination Survey (NHANES) database, we conducted a population-based cross-sectional 1,324 participants. MAFLD was defined as controlled attenuation parameter (CAP) score ≥ 248 dB/m accompanied by metabolic dysfunction. A median stiffness measurement 8.2 kPa used identify significant (≥ F2). Multivariable logistic regression employed assess impact of TyG on LF outcomes. restricted cubic spline (RCS) model explore nonlinear effects, receiver operating characteristic (ROC) curves were applied evaluate effectiveness predicting. Among participants, 716 men 608 women, aged 20 80 years, representing various racial groups. Significant observed 137 out After adjusting for confounding factors, higher significantly associated an increased incidence MAFLD-related (OR = 2.18, 95% CI, 1.14–4.18; p < 0.05). Elevated levels showed positive correlation fibrosis, odds ratio (OR) exceeding 1 when above 8.054. Subgroup analyses stratified sex, age, body mass (BMI) revealed differences after confounders. The stronger women 2.53, 1.16–5.53) than 1.95, 0.81–4.72). also found obesity status (overweight: OR 4.80, 1.27–18.2; obese: 2.26, 1.20–5.53). In patients 40–59, strongly 2.85, 1.16–6.79). Furthermore, area under ROC curve (AUC) predicting 0.73 (95% 0.68–0.78), indicating moderate predictive ability. general population, elevated positively risk patients.

Language: Английский

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