The gut microbiota‐astrocyte axis: Implications for type 2 diabetic cognitive dysfunction

CNS Neuroscience & Therapeutics, Год журнала: 2023, Номер 29(S1), С. 59 - 73

Опубликована: Янв. 4, 2023

Abstract Background Diabetic cognitive dysfunction (DCD) is one of the most insidious complications type 2 diabetes mellitus, which can seriously affect ability to self‐monitoring blood glucose and quality life in elderly. Previous pathological studies have focused on neuronal dysfunction, characterized by extracellular beta‐amyloid deposition intracellular tau hyperphosphorylation. In recent years, astrocytes been recognized as a potential therapeutic target for important participants central control metabolism. The disorder gut microbiota their metabolites linked series metabolic diseases such mellitus. imbalance intestinal flora has effect promoting occurrence deterioration several diabetes‐related complications. Gut microbes drive astrocyte activation. Aims We reviewed progress DCD related “gut microbiota‐astrocyte” axis terms peripheral inflammation, blood–brain barrier (BBB) systemic brain energy metabolism disorders deepen research explore targets. Conclusion “Gut axis, unique bidirectional crosstalk brain‐gut mediates intermediate process neurocognitive secondary

Язык: Английский

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The relationship between SGLT2 and systemic blood pressure regulation

Hypertension Research, Год журнала: 2024, Номер 47(8), С. 2094 - 2103

Опубликована: Май 23, 2024

Abstract The sodium-glucose cotransporter 2 (SGLT2) is a glucose transporter that located within the proximal tubule of kidney’s nephrons. While it typically associated with kidney, was later identified in various areas central nervous system, including modulating cardiorespiratory regulation like blood pressure. In SGLT2 functions by reabsorbing from nephron’s into bloodstream. inhibitors are medications hinder function SGLT2, thus preventing absorption and allowing for its excretion through urine. not first-line choice, they given conjunction other pharmaceutical interventions to manage hyperglycemia individuals diabetes mellitus. also have surprising secondary effect decreasing pressure independent levels. implication lowering presence system brings question role brain. Here, we evaluate review inhibitors, their control, future as antihypertensive agents, possible mechanisms control system.

Язык: Английский

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SGLT2 inhibitors: a novel therapy for cognitive impairment via multifaceted effects on the nervous system

Translational Neurodegeneration, Год журнала: 2024, Номер 13(1)

Опубликована: Авг. 9, 2024

The rising prevalence of diabetes mellitus has casted a spotlight on one its significant sequelae: cognitive impairment. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, originally developed for management, are increasingly studied their benefits. These benefits may include reduction oxidative stress and neuroinflammation, decrease amyloid burdens, enhancement neuronal plasticity, improved cerebral glucose utilization. multifaceted effects the relatively favorable side-effect profile SGLT2 inhibitors render them promising therapeutic candidate disorders. Nonetheless, application impairment is not without limitations, necessitating more comprehensive research to fully determine potential treatment. In this review, we discuss role in neural function, elucidate diabetes-cognition nexus, synthesize current knowledge based animal studies clinical evidence. Research gaps proposed spur further investigation.

Язык: Английский

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Assessment of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and other antidiabetic agents in Alzheimer’s disease: A population-based study

Pharmacological Research, Год журнала: 2024, Номер 206, С. 107295 - 107295

Опубликована: Июль 4, 2024

The lack of effective treatments for dementia has led to explore the potential antidiabetic agents as a possible approach. This cross-sectional and population-based study aimed investigate relationship between each drug their defined daily doses (DDDs) use anti-Alzheimer's disease (AD) drugs in order establish new hypotheses about role AD. For that purpose, database containing information on medications prescribed 233183 patients aged 50 years or older 2018 2020 was used. DDDs were calculated according ATC/DDD index 2023. Statistical analyses, with logistic regression, carried out assess anti-AD consumption. A total 91836 who at least one antihypertensive, antidiabetic, lipid-modifying agent included study; specifically, 29260 medication. Among agents, glucagon-like peptide-1 analogs (GLP-1) likely have positive association people 70 80 years. Additionally, sodium-glucose cotransporter 2 inhibitors (SGLT2i) prone usage across almost every age. However, insulin associated an increased agents. In conclusion, there is evidence suggesting correlation certain dementia. Specifically, GLP-1 SGLT2i might be lower odds usage, while insulins linked higher using drugs.

Язык: Английский

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The impact of sodium‐glucose co‐transporter‐2 inhibitors on dementia and cardiovascular events in diabetic patients with atrial fibrillation

Diabetes/Metabolism Research and Reviews, Год журнала: 2024, Номер 40(2)

Опубликована: Фев. 1, 2024

Abstract Aims The effectiveness of sodium‐glucose co‐transporter‐2 inhibitors (SGLT2i) on incident dementia in patients with diabetes and atrial fibrillation (AF) remains unknown. This study aimed to investigate the association between SGLT2i risk diabetic AF, explore interactions oral anticoagulants or dipeptidyl peptidase‐4 (DPP4i). Materials Methods We conducted a cohort using Taiwan's National Health Insurance Research Database. Patients AFwithout prior history established cardiovascular diseases, were identified. Using propensity score matching, 810 receiving matched 1620 not SGLT2i. primary outcome was dementia, secondary outcomes included composite events mortality. Results After up 5 years follow‐up, use associated significantly lower (hazard: 0.71, 95% confidence interval: 0.51–0.98), particularly vascular (HR: 0.44, CI: 0.24–0.82). related reduced risks AF‐related hospitalisation 0.72, 0.56–0.93), stroke 0.75, 0.60–0.94), all‐cause death 0.33, 0.24–0.44). protective effects consistent irrespective concurrent non‐vitamin K antagonist (NOACs) DPP4i. Conclusions In hospitalisation, stroke, death. independent either NOACs

Язык: Английский

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The immunomodulatory effects of GLP-1 receptor agonists in neurogenerative diseases and ischemic stroke treatment

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Март 11, 2025

Glucagon-like peptide-1 (GLP-1) receptor is widely distributed in the digestive system, cardiovascular adipose tissue and central nervous system. Numerous GLP-1 receptor-targeting drugs have been investigated clinical studies for various indications, including type 2 diabetes obesity (accounts 70% of total studies), non-alcoholic steatohepatitis, Alzheimer's disease, Parkinson's disease. This review presented fundamental information regarding two categories agonists (GLP-1RAs): peptide-based small molecule compounds, elaborated their potential neuroprotective effects by inhibiting neuroinflammation, reducing neuronal apoptosis, ultimately improving cognitive function neurodegenerative diseases. As a new hypoglycemic drug, GLP-1RA has unique role concurrent risk stroke T2D patients. Given infiltration peripheral immune cells into brain tissue, particularly areas surrounding infarct lesion, we further regulatory mechanisms. could not only facilitate M2 polarization microglia through both direct indirect pathways, but also modulate quantity T cell subtypes, CD4, CD8, cells, resulting inhibition inflammatory responses promotion regeneration interleukin-10 secretion. Therefore, believe that "Tregs-microglia-neuron/neural precursor cells" axis instrumental mediating suppression neuroprotection context ischemic stroke. benefits rapid diffusion, favorable blood-brain barrier permeability versatile administration routes, these compounds will be one important candidates GLP-1RA. We look forward to evidence intervention or complicated

Язык: Английский

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Efficacy and safety profile of SGLT2 inhibitors in the elderly: How is the benefit/risk balance?

Diabetes & Metabolism, Год журнала: 2023, Номер 49(2), С. 101419 - 101419

Опубликована: Янв. 11, 2023

Язык: Английский

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Diabetes-Alzheimer's connection in older age: SGLT2 inhibitors as promising modulators of disease pathways

Ageing Research Reviews, Год журнала: 2023, Номер 90, С. 102018 - 102018

Опубликована: Июль 20, 2023

Язык: Английский

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Iron and Ferroptosis More than a Suspect: Beyond the Most Common Mechanisms of Neurodegeneration for New Therapeutic Approaches to Cognitive Decline and Dementia

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(11), С. 9637 - 9637

Опубликована: Июнь 1, 2023

Neurodegeneration is a multifactorial process that involves multiple mechanisms. Examples of neurodegenerative diseases are Parkinson’s disease, sclerosis, Alzheimer’s prion such as Creutzfeldt–Jakob’s and amyotrophic lateral sclerosis. These progressive irreversible pathologies, characterized by neuron vulnerability, loss structure or function neurons, even demise in the brain, leading to clinical, functional, cognitive dysfunction movement disorders. However, iron overload can cause neurodegeneration. Dysregulation metabolism associated with cellular damage oxidative stress reported common event several diseases. Uncontrolled oxidation membrane fatty acids triggers programmed cell death involving iron, ROS, ferroptosis, promoting death. In content brain significantly increased vulnerable regions, resulting lack antioxidant defenses mitochondrial alterations. Iron interacts glucose reciprocally. Overall, accumulation ferroptosis play significant role, particularly context diabetes-induced decline. chelators improve performance, meaning control reduces neuronal promising novel therapeutic approach impairment.

Язык: Английский

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The role of autophagy in the treatment of type II diabetes and its complications: a review

Frontiers in Endocrinology, Год журнала: 2023, Номер 14

Опубликована: Сен. 21, 2023

Type II diabetes mellitus (T2DM) is a chronic metabolic disease characterized by prolonged hyperglycemia and insulin resistance (IR). Its incidence increasing annually, posing significant threat to human life health. Consequently, there an urgent requirement discover effective drugs investigate the pathogenesis of T2DM. Autophagy plays crucial role in maintaining normal islet structure. However, state high glucose, autophagy inhibited, resulting impaired function, resistance, complications. Studies have shown that modulating through activation or inhibition can positive impact on treatment T2DM its it important note specific regulatory mechanisms vary depending target organ. This review explores T2DM, taking into account both genetic external factors. It also provides summary reported chemical traditional Chinese medicine autophagic pathway for

Язык: Английский

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