The Role of Insulin Resistance in Fueling NAFLD Pathogenesis: From Molecular Mechanisms to Clinical Implications

Journal of Clinical Medicine, Год журнала: 2022, Номер 11(13), С. 3649 - 3649

Опубликована: Июнь 24, 2022

Non-alcoholic fatty liver disease (NAFLD) represents a predominant hepatopathy that is rapidly becoming the most common cause of hepatocellular carcinoma worldwide. The close association with metabolic syndrome’s extrahepatic components has suggested nature systemic metabolic-related disorder based on interplay between genetic, nutritional, and environmental factors, creating complex network yet-unclarified pathogenetic mechanisms in which role insulin resistance (IR) could be crucial. This review detailed clinical evidence involved NAFLD–IR relationship, presenting both classic more innovative models. In particular, we focused reciprocal effects IR, oxidative stress, inflammation insulin-sensitivity disruption critical regions such as hepatic adipose tissue, while considering impact genetics/epigenetics regulation IR well nutrients specific insulin-related gene expression (nutrigenetics nutrigenomics). addition, discussed emerging capability gut microbiota to interfere physiological signaling hormonal pathways responsible for maintaining homeostasis by inducing an abnormal activation immune system. translation these novel findings into practice promote expansion accurate diagnostic/prognostic stratification tools tailored pharmacological approaches.

Язык: Английский

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Insulin resistance in ischemic stroke: Mechanisms and therapeutic approaches

Frontiers in Endocrinology, Год журнала: 2022, Номер 13

Опубликована: Дек. 15, 2022

The pathological condition of insulin resistance prevents the neuroprotective effects insulin. Numerous studies have demonstrated that resistance, as an independent risk factor for ischemic stroke, accelerates formation thrombosis and promotes development atherosclerosis, both which are major mechanisms stroke. Additionally, negatively affects prognosis patients with stroke regardless whether patient has diabetes, but not well studied. We explored association between primary brain injury in (inflammation, oxidative stress, neuronal damage), looking potential causes poor due to resistance. Furthermore, we summarize therapeutic approaches propose new directions clinically improving

Язык: Английский

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The Metabolic Score for Insulin Resistance (METS-IR) Predicts Cardiovascular Disease and Its Subtypes in Patients with Hypertension and Obstructive Sleep Apnea

Clinical Epidemiology, Год журнала: 2023, Номер Volume 15, С. 177 - 189

Опубликована: Фев. 1, 2023

We aimed to evaluate the METS-IR (metabolic score for insulin resistance) index prediction of incident cardiovascular disease (CVD) and its subtypes (coronary artery stroke) in patients with hypertension obstructive sleep apnea (OSA).A retrospective cohort study was conducted 2031 adults OSA, participants from Urumqi Research on Sleep Apnea Hypertension (UROSAH). The hazard ratios 95% CIs (credibility interval) CVD were estimated using multivariate Cox proportional hazards regression models.After a median follow-up 6.80 years (interquartile range: 5.90-8.00 years), total 317 (15.61%) developed new-onset CVD, including 198 (9.75%) coronary heart (CHD) 119 (5.86%) stroke. After adjusting as many relevant confounding factors possible, each SD increase associated 30% increased risk new onset overall events, 32% CHD, 27% When assessed tertiles, after adjustment fully factors, highest tertiles versus lowest greater (HR 2.05; CI 1.52,-2.77), CHD 1.96; 1.35-2.84), stroke 2.24; 1.35-3.72). results various subgroups sensitivity analyses similar. added, predictions reclassified identified more accurately than baseline models C-index, continuous net reclassification improvement, integrated discrimination index. showed similar results.METS-IR is powerful predictor which can facilitate identification high-risk individuals provide individualized prevention.

Язык: Английский

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Adipose-derived Mesenchymal Stem Cells Therapy as a new Treatment Option for Diabetes Mellitus

The Journal of Clinical Endocrinology & Metabolism, Год журнала: 2023, Номер 108(8), С. 1889 - 1897

Опубликована: Март 14, 2023

Abstract The worldwide increase in the prevalence of diabetes mellitus has raised demand for new therapeutic strategies targeting diabetic symptoms and its chronic complications. Among different treatment options diabetes, adipose-derived mesenchymal stem cells (ADMSCs) therapy attract most attention. effects ADMSCs are based primarily on their paracrine release immunomodulatory, anti-inflammatory, trophic factors. Animal models as well human clinical trials have shown that can effectively facilitate endogenous β cell regeneration, preserve residual mass, reduce islet graft rejection, regulate immune system, ultimately improve insulin sensitivity or ameliorate resistance peripheral tissues. Nevertheless, transplantation is associated with certain risks; therefore recently much attention been devoted to derivatives, such exosomes conditioned media, agents diabetes. Compared ADMSCs, cell-free even better potential. This narrative review summarizes recent outcomes molecular mechanisms action both type 1 DM 2 DM, shows feasibility, benefits, current limitations.

Язык: Английский

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White Adipose Tissue Dysfunction: Pathophysiology and Emergent Measurements

Nutrients, Год журнала: 2023, Номер 15(7), С. 1722 - 1722

Опубликована: Март 31, 2023

White adipose tissue (AT) dysfunction plays an important role in the development of cardiometabolic alterations associated with obesity. AT is characterized by loss expansion capacity AT, increment adipocyte hypertrophy, and changes secretion profile cells, accumulation macrophages inflammation. Since not all people excess adiposity develop comorbidities, it necessary to find simple tools that can evidence allow detection those potential metabolic alterations. This review focuses on current pathophysiological mechanisms white emerging measurements assess its functionality.

Язык: Английский

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Roles of endoplasmic reticulum stress in the pathophysiology of polycystic ovary syndrome

Frontiers in Endocrinology, Год журнала: 2023, Номер 14

Опубликована: Фев. 15, 2023

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-age women, affecting up to 15% of women in this group, and cause anovulatory infertility. Although its etiology remains unclear, recent research has revealed critical role endoplasmic reticulum (ER) stress pathophysiology PCOS. ER defined as a condition which unfolded or misfolded proteins accumulate because an imbalance demand for protein folding protein-folding capacity ER. results activation several signal transduction cascades, collectively termed response (UPR), regulates various cellular activities. In principle, UPR restores homeostasis keeps cell alive. However, if cannot be resolved, it induces programmed death. recently been recognized play diverse roles both physiological pathological conditions ovary. review, we summarize current knowledge pathogenesis pathways are activated ovaries mouse model PCOS humans, local hyperandrogenism follicular microenvironment associated with responsible activating these. The contributes through multiple effects granulosa cells. Finally, discuss potential serve novel therapeutic target

Язык: Английский

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An Update on the Molecular and Cellular Basis of Pharmacotherapy in Type 2 Diabetes Mellitus

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(11), С. 9328 - 9328

Опубликована: Май 26, 2023

Diabetes mellitus (DM) is a chronic illness with an increasing global prevalence. More than 537 million cases of diabetes were reported worldwide in 2021, and the number steadily increasing. The people suffering from DM projected to reach 783 2045. In 2021 alone, more USD 966 billion was spent on management DM. Reduced physical activity due urbanization believed be major cause increase incidence disease, as it associated higher rates obesity. poses risk for complications such nephropathy, angiopathy, neuropathy retinopathy. Hence, successful blood glucose cornerstone therapy. effective hyperglycemia type 2 includes exercise, diet therapeutic interventions (insulin, biguanides, second generation sulfonylureas, glucagon-like peptide 1 agonists, dipeptidyl-peptidase 4 inhibitors, thiazolidinediones, amylin mimetics, meglitinides, α-glucosidase sodium-glucose cotransporter-2 inhibitors bile acid sequestrants). optimal timely treatment improves quality life reduces severe burden disease patients. Genetic testing, examining roles different genes involved pathogenesis DM, may also help achieve future by reducing enhancing use individualized regimens.

Язык: Английский

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The relationship between HMGB1 and autophagy in the pathogenesis of diabetes and its complications

Frontiers in Endocrinology, Год журнала: 2023, Номер 14

Опубликована: Март 29, 2023

Diabetes mellitus is a chronic metabolic disorder characterized by elevated blood glucose levels and has become the third leading threat to human health after cancer cardiovascular disease. Recent studies have shown that autophagy closely associated with diabetes. Under normal physiological conditions, promotes cellular homeostasis, reduces damage healthy tissues bidirectional effects on regulating However, under pathological unregulated activation leads cell death may contribute progression of Therefore, restoring be key strategy treat High-mobility group box 1 protein (HMGB1) chromatin mainly present in nucleus can actively secreted or passively released from necrotic, apoptotic, inflammatory cells. HMGB1 induce activating various pathways. Studies plays an important role insulin resistance In this review, we will introduce biological structural characteristics summarize existing knowledge relationship between HMGB1, autophagy, diabetes, diabetic complications. We also potential therapeutic strategies useful for prevention treatment diabetes its

Язык: Английский

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Changes in Cells Associated with Insulin Resistance

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(4), С. 2397 - 2397

Опубликована: Фев. 18, 2024

Insulin is a polypeptide hormone synthesized and secreted by pancreatic β-cells. It plays an important role as metabolic hormone. influences the metabolism of glucose, regulating plasma glucose levels stimulating storage in organs such liver, muscles adipose tissue. involved fat metabolism, increasing triglycerides decreasing lipolysis. Ketone body also depends on insulin action, reduces ketone concentrations protein metabolism. increases nitrogen retention, facilitates transport amino acids into cells synthesis proteins. inhibits breakdown cellular growth proliferation. On other hand, defects intracellular signaling pathways may cause several disturbances human resulting chronic diseases. resistance, known impaired sensitivity, due to decreased reaction for levels, seen when use response adequate concentration impaired. resistance cause, example, increased levels. That state, called hyperinsulinemia, impairs processes observed patients with type 2 diabetes mellitus obesity. Hyperinsulinemia increase risk initiation, progression metastasis cancers poor cancer outcomes. health problem worldwide; therefore, mechanisms causes types strategies against are described this review. Attention paid factors that associated development main characteristic symptoms particular syndromes, plus aspects severe resistance. This review mainly focuses description analysis changes

Язык: Английский

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Impact of Lipids on Insulin Resistance: Insights from Human and Animal Studies

Drug Design Development and Therapy, Год журнала: 2024, Номер Volume 18, С. 3337 - 3360

Опубликована: Июль 1, 2024

Insulin resistance (IR) is a complex pathological condition central to metabolic diseases such as type 2 diabetes mellitus (T2DM), cardiovascular disease, non-alcoholic fatty liver and polycystic ovary syndrome (PCOS). This review evaluates the impact of lipids on insulin by analyzing findings from human animal studies. The articles were searched PubMed database using two keywords: (1) "Role Lipids AND Resistance Humans" (2) Animal Models". Studies in humans revealed that elevated levels free acids (FFAs) triglycerides (TGs) are closely associated with reduced sensitivity, interventions like metformin omega-3 show potential benefits. In models, high-fat diets disrupt signaling increase inflammation, lipid mediators diacylglycerol (DAG) ceramides playing significant roles. DAG activates protein kinase C, which eventually impairs signaling, while inhibit Akt/PKB, further contributing IR. Understanding these mechanisms crucial for developing effective prevention treatment strategies IR-related diseases.

Язык: Английский

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