Molecular Mechanisms Linking Oxidative Stress and Diabetes Mellitus

Oxidative Medicine and Cellular Longevity, Journal Year: 2020, Volume and Issue: 2020, P. 1 - 13

Published: March 9, 2020

Type 2 diabetes mellitus (T2DM) is the most prevalent metabolic disorder characterized by chronic hyperglycemia and an inadequate response to circulatory insulin peripheral tissues resulting in resistance. Insulin resistance has a complex pathophysiology, it contributed multiple factors including oxidative stress. Oxidative stress refers imbalance between free radical production antioxidant system leading reduction of sensitivity contributing development T2DM via several molecular mechanisms. In this review, we present mechanisms which milieu contributes pathophysiology mellitus.

Language: Английский

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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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Diabetic vascular diseases: molecular mechanisms and therapeutic strategies

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: April 10, 2023

Abstract Vascular complications of diabetes pose a severe threat to human health. Prevention and treatment protocols based on single vascular complication are no longer suitable for the long-term management patients with diabetes. Diabetic panvascular disease (DPD) is clinical syndrome in which vessels various sizes, including macrovessels microvessels cardiac, cerebral, renal, ophthalmic, peripheral systems diabetes, develop atherosclerosis as common pathology. Pathological manifestations DPDs usually manifest macrovascular atherosclerosis, well microvascular endothelial function impairment, basement membrane thickening, microthrombosis. Cardiac, microangiopathy coexist microangiopathy, while renal retinal predominantly microangiopathic. The following associations exist between DPDs: numerous similar molecular mechanisms, risk-predictive relationships diseases. Aggressive glycemic control combined early comprehensive intervention key prevention treatment. In addition widely recommended metformin, glucagon-like peptide-1 agonist, sodium-glucose cotransporter-2 inhibitors, latest aldose reductase peroxisome proliferator-activated receptor-γ agonizts, glucokinases mitochondrial energy modulators, etc. under active development. proposed obtain more systematic care requires center focusing This would leverage advantages cross-disciplinary approach achieve better integration pathogenesis therapeutic evidence. Such strategy confer benefits promote development DPD discipline.

Language: Английский

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Hyperglycemia and Oxidative Stress: An Integral, Updated and Critical Overview of Their Metabolic Interconnections

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(11), P. 9352 - 9352

Published: May 27, 2023

This review focuses on the multiple and reciprocal relationships that exist between oxidative stress, hyperglycemia diabetes related metabolic disorders. Human metabolism uses most of consumed glucose under aerobic conditions. Oxygen is needed in mitochondria to obtain energy, as well for action microsomal oxidases cytosolic pro-oxidant enzymes. relentlessly generates a certain amount reactive oxygen species (ROS). Although ROS are intracellular signals necessary some physiological processes, their accumulation leads hyperglycemia, progressive resistance insulin. A cellular versus an antioxidant equilibrium would regulate levels, but pro-inflammatory conditions feed back each other relevance interconnections tends increase those Hyperglycemia promotes collateral through protein kinase C, polyols hexosamine routes. In addition, it also facilitates spontaneous auto-oxidation formation advanced glycation end products (AGEs), which turn interact with receptors (RAGE). The mentioned processes undermine structures, finally giving place progressively greater degree stress further alterations, complications. NFκB major transcription factor involved expression mediators, while Nrf2 regulating response. FoxO equilibrium, its role controversial. summarizes key factors linking diverse routes enhanced vice versa, emphasizing desirable balance proteins.

Language: Английский

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Insulin–PI3K signalling: an evolutionarily insulated metabolic driver of cancer

Nature Reviews Endocrinology, Journal Year: 2020, Volume and Issue: 16(5), P. 276 - 283

Published: March 3, 2020

Language: Английский

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Diabetes and Sarcopenic Obesity: Pathogenesis, Diagnosis, and Treatments

Frontiers in Endocrinology, Journal Year: 2020, Volume and Issue: 11

Published: Aug. 25, 2020

Sarcopenic obesity and diabetes are two increasing health problems worldwide, which both share many common risk factors, such as aging general obesity. The pathogenesis of sarcopenic includes aging, physical inactivity, malnutrition, low-grade inflammation, insulin resistance, hormonal changes. Nevertheless, there major forms to cause diabetes: impaired secretion action. Furthermore, the individual diagnosis sarcopenia should be combined adequately define Also, fasting plasma glucose test (FPG), two-hour oral tolerance (OGTT), glycated hemoglobin (A1C), random coupled with symptoms. Healthy diet activity beneficial diabetes, but only recommended drugs for diabetes. This review consolidates discusses latest research in pathogenesis, diagnosis, treatments

Language: Английский

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Nanodelivery of Natural Antioxidants: An Anti-aging Perspective

Frontiers in Bioengineering and Biotechnology, Journal Year: 2020, Volume and Issue: 7

Published: Jan. 9, 2020

The aging process is known to be associated with heightened oxidative stress and related systemic inflammation. Therefore, antioxidant supplementation regarded as a promising strategy combat pathological conditions. Food-grade antioxidants from plant-derived extracts are the most common ingredients of these supplements. Phyto-bioactive compounds such curcumin, resveratrol, catechins, quercetin among commonly applied natural used potential modulators free radical-induced cellular damages. therapeutic is, however, restricted by their low bioavailability poor solubility, stability absorbance in gastrointestinal tract. Recently, novel nanotechnology-based systems were developed for delivery improved and, consequently, efficacy clinical practice. Such have provided many benefits preclinical research over conventional preparations, including superior solubility stability, extended half-life, epithelium permeability bioavailability, enhanced tissue targeting minimized side effects. present review summarizes recent developments nanodelivery its application conditions stress.

Language: Английский

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The Role of Estrogen in Insulin Resistance

American Journal Of Pathology, Journal Year: 2021, Volume and Issue: 191(9), P. 1490 - 1498

Published: June 5, 2021

Language: Английский

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Mechanisms of Non-Alcoholic Fatty Liver Disease in the Metabolic Syndrome. A Narrative Review

Antioxidants, Journal Year: 2021, Volume and Issue: 10(2), P. 270 - 270

Published: Feb. 10, 2021

Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) are two different entities sharing common clinical physio-pathological features, with insulin resistance (IR) as the most relevant. Large evidence leads to consider it a risk factor for cardiovascular disease, regardless of age, sex, smoking habit, cholesterolemia, other elements MS. Therapeutic strategies remain still unclear, but lifestyle modifications (diet, physical exercise, weight loss) determine an improvement in IR, MS, both histologic picture. NAFLD IR bidirectionally correlated and, consequently, development pre-diabetes diabetes is direct consequence at extrahepatic level. In turn, type 2 well-known multiorgan damage, including involvement system, kidney peripheral nervous system. The increased MS incidence worldwide, above all due changes diet lifestyle, associated equally significant increase NAFLD, subsequent rise morbidity mortality metabolic, hepatic diseases. Therefore, slowdown "bad company" constituted by consequent indirect costs, represents one main challenges National Health Systems.

Language: Английский

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Insulin Signal Transduction Perturbations in Insulin Resistance

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(16), P. 8590 - 8590

Published: Aug. 10, 2021

Type 2 diabetes mellitus is a widespread medical condition, characterized by high blood glucose and inadequate insulin action, which leads to resistance. Insulin resistance in insulin-responsive tissues precedes the onset of pancreatic β-cell dysfunction. Multiple molecular pathophysiological mechanisms are involved consequence complex combination metabolic disorders, lipotoxicity, glucotoxicity, inflammation. There ample evidence linking different mechanistic approaches as cause resistance, but no central mechanism yet described an underlying reason behind this condition. This review combines interlinks defects signal transduction pathway state with special emphasis on AGE-RAGE-NF-κB axis. Here, we describe important factors that play crucial role pathogenesis provide directionality for events. The interplay inflammation oxidative stress decline through IAPP-RAGE induced toxicity also addressed. Overall, generating comprehensive overview plethora focus establishment unifying new insights future interventions type mellitus.

Language: Английский

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