Oxidative stress in the pathophysiology of type 2 diabetes and related complications: Current therapeutics strategies and future perspectives

Free Radical Biology and Medicine, Journal Year: 2022, Volume and Issue: 184, P. 114 - 134

Published: April 7, 2022

Type 2 diabetes (T2DM) is a persistent metabolic disorder rising rapidly worldwide. It characterized by pancreatic insulin resistance and β-cell dysfunction. Hyperglycemia induced reactive oxygen species (ROS) production oxidative stress are correlated with the pathogenesis progression of this disease. To counteract harmful effects ROS, endogenous antioxidants body or exogenous neutralise it maintain bodily homeostasis. Under hyperglycemic conditions, imbalance between cellular antioxidant system ROS results in stress, which subsequently development diabetes. These produced endoplasmic reticulum, phagocytic cells peroxisomes, mitochondrial electron transport chain (ETC) playing pivotal role. The exacerbated can directly cause structural functional modifications proteins, lipids nucleic acids. also modulates several intracellular signaling pathways that lead to impairment function. In addition, hyperglycemia-induced contributes micro- macro-vascular diabetic complications. Various in-vivo in-vitro studies have demonstrated anti-oxidative natural products their derived bioactive compounds. However, there conflicting clinical evidence on beneficial these therapies prevention. This review article focused multifaceted role caused overproduction related complications possible antioxidative therapeutic strategies targeting

Language: Английский

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Mechanisms underlying the pathophysiology of type 2 diabetes: From risk factors to oxidative stress, metabolic dysfunction, and hyperglycemia

Mutation Research/Genetic Toxicology and Environmental Mutagenesis, Journal Year: 2021, Volume and Issue: 874-875, P. 503437 - 503437

Published: Dec. 14, 2021

Language: Английский

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The paradigm change from reactive medical services to 3PM in ischemic stroke: a holistic approach utilising tear fluid multi-omics, mitochondria as a vital biosensor and AI-based multi-professional data interpretation

The EPMA Journal, Journal Year: 2024, Volume and Issue: 15(1), P. 1 - 23

Published: Feb. 27, 2024

Worldwide stroke is the second leading cause of death and third disability combined. The estimated global economic burden by over US$891 billion per year. Within three decades (1990-2019), incidence increased 70%, deaths 43%, prevalence 102%, DALYs 143%. Of 100 million people affected stroke, about 76% are ischemic (IS) patients recorded worldwide. Contextually, moves into particular focus multi-professional groups including researchers, healthcare industry, economists, policy-makers. Risk factors demonstrate sufficient space for cost-effective prevention interventions in primary (suboptimal health) secondary (clinically manifested collateral disorders contributing to risks) care. These risks interrelated. For example, sedentary lifestyle toxic environment both mitochondrial stress, systemic low-grade inflammation accelerated ageing; inflammageing a associated with ageing poor outcomes. Stress overload, decreased bioenergetics hypomagnesaemia vasospasm lesions heart brain all age teenagers. Imbalanced dietary patterns folate but rich red processed meat, refined grains, sugary beverages hyperhomocysteinaemia, inflammation, small vessel disease, IS risks. Ongoing 3PM research towards vulnerable population promoted European Association Predictive, Preventive Personalised Medicine (EPMA) demonstrates promising results holistic patient-friendly non-invasive approach utilising tear fluid-based health risk assessment, mitochondria as vital biosensor AI-based data interpretation reported here EPMA expert group. Collected that IS-relevant corresponding molecular pathways examples, there an evident overlap between involved diabetic retinopathy early indicator patients. Just exemplify some them such 5-aminolevulinic acid/pathway, which also characteristic altered mitophagy patterns, insomnia, stress regulation modulation microbiota-gut-brain crosstalk. Further, ceramides considered mediators oxidative cardiometabolic negatively affecting respiratory chain function fission/fusion activity, sleep-wake behaviour, vascular stiffness remodelling. Xanthine/pathway homeostasis stress-driven anxiety-like behaviour well mechanisms arterial stiffness. In order assess individual risks, application machine learning (AI tool) essential accurate performed multiparametric analysis. Aspects presented paper include needs young populations elderly, personalised assessment care, cost-efficacy, innovative technologies screening programmes, advanced education measures professionals general population-all pillars paradigm change from reactive medical services overall management EPMA.

Language: Английский

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Plant Secondary Metabolites as Modulators of Mitochondrial Health: An Overview of Their Anti-Oxidant, Anti-Apoptotic, and Mitophagic Mechanisms

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(1), P. 380 - 380

Published: Jan. 4, 2025

Plant secondary metabolites (PSMs) are a diverse group of bioactive compounds, including flavonoids, polyphenols, saponins, and terpenoids, which have been recognised for their critical role in modulating cellular functions. This review provides comprehensive analysis the effects PSMs on mitochondrial health, with particular emphasis therapeutic potential. Emerging evidence shows that these improve function by reducing oxidative stress, promoting biogenesis, regulating key processes such as apoptosis mitophagy. Mitochondrial dysfunction, hallmark many pathologies, neurodegenerative disorders, cardiovascular diseases, metabolic syndrome, has shown to benefit from protective PSMs. Recent studies show can dynamics, stabilise membranes, enhance bioenergetics, offering significant promise prevention treatment mitochondrial-related diseases. The molecular mechanisms underlying effects, modulation signalling pathways direct interactions proteins, discussed. integration into strategies is highlighted promising avenue improving efficacy while minimising side commonly associated synthetic drugs. also highlights need future research elucidate specific roles individual synergistic within complex plant matrices, may further optimise utility. Overall, this work valuable insights health potential natural agents targeting dysfunction.

Language: Английский

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Sarcopenia Is a Cause and Consequence of Metabolic Dysregulation in Aging Humans: Effects of Gut Dysbiosis, Glucose Dysregulation, Diet and Lifestyle

Cells, Journal Year: 2022, Volume and Issue: 11(3), P. 338 - 338

Published: Jan. 20, 2022

Skeletal muscle mass plays a critical role in healthy lifespan by helping to regulate glucose homeostasis. As seen sarcopenia, decreased skeletal impairs homeostasis, but it may also be caused dysregulation. Gut microbiota modulates lipopolysaccharide (LPS) production, short-chain fatty acids (SCFA), and various metabolites that affect the host metabolism, including tissues, have sarcopenia etiology. Here, we aimed review relationship between mass, gut microbiota, effect of consuming probiotics prebiotics on development pathological consequences aging human population. This includes discussions about effects metabolism interaction dietary intake, physical activity, microbiome influence through modulating gut–muscle axis. Emerging evidence suggests can both function, part metabolisms branch-chain amino might act directly humans or indirectly brain liver. Dietary factors such as fats, proteins, indigestible carbohydrates lifestyle interventions exercise, smoking, alcohol intake help hinder putative The presented this loss function are not an inevitable consequence process, prevent delay sarcopenia.

Language: Английский

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Mitochondrial Dysfunction in Vascular Wall Cells and Its Role in Atherosclerosis

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(16), P. 8990 - 8990

Published: Aug. 20, 2021

Altered mitochondrial function is currently recognized as an important factor in atherosclerosis initiation and progression. Mitochondrial dysfunction can be caused by DNA (mtDNA) mutations, which inherited or spontaneously acquired various organs tissues, having more less profound effects depending on the tissue energy status. Arterial wall cells are among most vulnerable to due their barrier metabolic functions. In atherosclerosis, mitochondria cause alteration of cellular metabolism respiration known produce excessive amounts reactive oxygen species (ROS) resulting oxidative stress. These processes involved vascular disease chronic inflammation associated with atherosclerosis. Currently, list mtDNA mutations human pathologies growing, many identified variants being tested markers. Alleviation stress appears promising for treatment. this review, we discuss role development, focusing key cell types arterial pathological processes. Accumulation isolated cells, such endothelial may contribute development local inflammatory process that helps explaining focal distribution atherosclerotic plaques surface. We also antioxidant anti-inflammatory approaches potentially reduce impact dysfunction.

Language: Английский

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Mitochondrial Dysfunction as a Factor of Energy Metabolism Disorders in Type 2 Diabetes Mellitus

Frontiers in Bioscience-Scholar, Journal Year: 2024, Volume and Issue: 16(1), P. 5 - 5

Published: March 8, 2024

The pathogenesis of type 2 diabetes mellitus (T2DM) is based on the development insulin resistance, which a disruption to ability tissues bind insulin, leading general metabolic disorder. Mitochondria are main participants in cellular energy metabolism, meaning their dysfunction associated with resistance T2DM. Mitochondrial function affected by various tissues, including skeletal muscle and liver, greatly influence glucose homeostasis throughout body. This review studies mitochondrial T2DM its impact disease progression. In addition, it considers causes underlying T2DM, mutations genome, DNA methylation, other epigenetic influences, as well impaired membrane potential. New therapeutic strategies for that have been developed target mitochondria will also be presented.

Language: Английский

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EPA and DHA differentially improve insulin resistance by reducing adipose tissue inflammation—targeting GPR120/PPARγ pathway

The Journal of Nutritional Biochemistry, Journal Year: 2024, Volume and Issue: 130, P. 109648 - 109648

Published: April 15, 2024

Language: Английский

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Impairment of Mitochondrial Respiration in Metabolic Diseases: An Overview

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(16), P. 8852 - 8852

Published: Aug. 9, 2022

Mitochondrial dysfunction has emerged as a central pathomechanism in the setting of obesity and diabetes mellitus, linking these intertwined pathologies that share insulin resistance common denominator. High-resolution respirometry (HRR) is state-of-the-art research method currently used to study mitochondrial respiration its impairment health disease. Tissue samples, cells or isolated mitochondria are exposed various substrate-uncoupler-inhibitor-titration protocols, which allows measurement calculation several parameters respiration. In this review, we discuss alterations bioenergetics main dysfunctional organs contribute development obese diabetic phenotypes both animal models human subjects. Herein review data regarding oxidative phosphorylation integrated function assessed by means HRR. We acknowledge critical role determining occurring early stages metabolic pathologies. conclude there mutual two-way relationship between insensitivity characterizes diseases.

Language: Английский

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Insulin Resistance in Mitochondrial Diabetes

Biomolecules, Journal Year: 2023, Volume and Issue: 13(1), P. 126 - 126

Published: Jan. 7, 2023

Mitochondrial diabetes (MD) is generally classified as a genetic defect of β-cells. The main pathophysiology insulin secretion failure in pancreatic β-cells due to impaired mitochondrial ATP production. However, several reports have mentioned the presence resistance (IR) clinical feature MD. As dysfunction one important factors causing IR, we need focus on IR another In this special issue, first briefly summarized signaling and molecular mechanisms IR. Second, overviewed currently confirmed pathogenic DNA (mtDNA) mutations from MITOMAP database. variants were mostly point transfer RNA (tRNA) genome. Third, focused these leading recently described “tRNA modopathies” reviewed features patients with diabetes. Finally, discussed MD caused by mtDNA explored possible mechanism underlying development This review should be beneficial all clinicians involved diagnostics therapeutics related diseases.

Language: Английский

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