Contemporary Endocrinology, Год журнала: 2023, Номер unknown, С. 55 - 77
Опубликована: Янв. 1, 2023
Язык: Английский
Cardiovascular Diabetology, Год журнала: 2024, Номер 23(1)
Опубликована: Июнь 28, 2024
Abstract Background Sodium-glucose cotransporter 2 inhibitors (SGLT-2i) are glucose-lowering agents used for the treatment of type diabetes mellitus, which also improve heart failure and decrease risk cardiovascular complications. Epicardial adipose tissue (EAT) dysfunction was suggested to contribute development failure. We aimed elucidate a possible role changes in EAT metabolic inflammatory profile beneficial cardioprotective effects SGLT-2i subjects with severe Methods 26 failure, reduced ejection fraction, treated versus without treatment, matched age (54.0 ± 2.1 vs. 55.3 years, n.s.), body mass index (27.8 0.9 28.8 1.0 kg/m , n.s.) left ventricular fraction (20.7 0.5 23.2 1.7%, who were scheduled transplantation or mechanical support implantation, included study. A complex metabolomic gene expression analysis obtained during surgery performed. Results ameliorated inflammation, as evidenced by improved pro-inflammatory genes decreased infiltration immune cells into EAT. Enrichment ether lipids oleic acid noted on suggests disposition ferroptosis, potentially further contributing oxidative stress subjects. Conclusions Our results show inflammation patients SGLT-2i, compared this therapy. Modulation status could represent novel mechanism behind SGLT-2i-associated
Язык: Английский
Процитировано
10
International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(4), С. 1670 - 1670
Опубликована: Фев. 15, 2025
A growing body of evidence indicates that nonglycemic effects sodium-glucose cotransporter 2 (SGLT2) inhibitors play an important role in the protective these drugs diabetes, chronic kidney disease, and heart failure. In recent years, anti-inflammatory potential SGLT2 has been actively studied. This review summarizes results clinical experimental studies on activity inhibitors, with a special focus their macrophages, key drivers metabolic inflammation. patients type therapy reduces levels inflammatory mediators. diabetic non-diabetic animal models, control low-grade inflammation by suppressing activation tissue recruitment monocytes from bloodstream, macrophage polarization towards M1 phenotype. The molecular mechanisms macrophages include attenuation inflammasome inhibition TLR4/NF-κB pathway, as well modulation other signaling pathways (AMPK, PI3K/Akt, ERK 1/2-MAPK, JAKs/STAT). discusses state-of-the-art concepts prospects further investigations are needed to obtain deeper insight into underlying molecular, cellular, physiological levels.
Язык: Английский
Процитировано
2
Experimental & Molecular Medicine, Год журнала: 2023, Номер 55(9), С. 1955 - 1973
Опубликована: Сен. 1, 2023
Abstract Adipose tissue is a dynamic and metabolically active organ that plays crucial role in energy homeostasis endocrine function. Recent advancements lipidomics techniques have enabled the study of complex lipid composition adipose its metabolic disorders such as obesity, diabetes, cardiovascular disease. In addition, has emerged powerful tool for understanding molecular mechanisms underlying these identifying bioactive mediators potential therapeutic targets. This review aims to summarize recent studies investigated remodeling lipids response specific physiological changes, pharmacological interventions, pathological conditions. We discuss explore identification generated regulate adipocytes systemic metabolism. propose manipulating lipid-mediator metabolism could serve approach preventing or treating obesity-related diseases.
Язык: Английский
Процитировано
22
Biomedicines, Год журнала: 2024, Номер 12(7), С. 1386 - 1386
Опубликована: Июнь 21, 2024
Cardiovascular disease (CVD) and kidney are the main causes of morbidity mortality in type 2 diabetes mellitus (T2DM). Globally, incidence T2DM continues to rise. A substantial increase burden CVD renal disease, alongside socioeconomic implications, would be anticipated. Adopting a purely glucose-centric approach focusing only on glycemic targets is no longer adequate mitigate cardiovascular risks T2DM. In past decade, significant advancement has been achieved expanding pharmaceutical options for T2DM, with novel agents such as sodium-glucose cotransporter (SGLT2) inhibitors glucagon-like peptide receptor agonists (GLP-1 RAs) demonstrating robust evidence cardiorenal protection. Combinatorial approaches comprising multiple pharmacotherapies combined single agent an emerging promising way not enhance patient adherence improve control but also achieve potential synergistic effects greater this review, we provide update antidiabetic appraisal mechanisms contributing Additionally, offer glimpse into landscape management near future by providing comprehensive summary upcoming early-phase trials.
Язык: Английский
Процитировано
4
Frontiers in Endocrinology, Год журнала: 2025, Номер 15
Опубликована: Янв. 21, 2025
Introduction A long-term high-fat diet (HFD) cause obesity and infertility through hypothalamic inflammation insulin resistance, leading to metabolic abnormalities ovulation dysfunction. The sodium-glucose cotransporter 2 inhibitors (SGLT2i) have emerged as a treatment for type diabetic patients, regulating adipose tissue metabolism, inflammation, in women with polycystic ovary syndrome (PCOS). study aimed investigate the pharmacological effects of dapagliflozin on improving energy sex hormones, fertility female mice following prolonged consumption HFD. Methods At 6 weeks age, were fed HFD treated dapagliflozin. Serum hormone concentrations inflammatory factors aged 28 or 38 quantified using ultrasensitive enzyme-linked immunosorbent assays (ELISAs). Metabolic parameters also assessed documented at different stages experiment. 34 half experimental each four groups standard chow mated male mice. Pregnancy rate, abortion pregnancy-related deaths, perinatal outcomes systematically recorded. Results After 16 feeding, significantly attenuated visceral fat deposition, weight gain, glucose intolerance, resistance induced by diet. However, these diminished after 32 weeks. Unexpectedly, neither nor elicited any significant changes serum IL-6 TNFα levels. Throughout experiment period, exhibited favorable reproductive function along sensitivity luteinizing (LH) release from pituitary gland. Discussion In conclusion, this demonstrates that alleviated HFD-induced dysfunction independently obesity, peripheral systemic suggesting its potential promising diet-related disorders.
Язык: Английский
Процитировано
0
Medicina, Год журнала: 2025, Номер 61(4), С. 613 - 613
Опубликована: Март 27, 2025
Background and Objectives: Type 2 diabetes (T2D) prediabetes represent major global health concerns, with obesity being a key risk factor. However, recent evidence suggests that the adipose tissue composition distribution play more critical role in metabolic dysfunction than total body weight or mass index (BMI). This study evaluates predictive capacity of Córdoba Equation for Estimating Body Fat (ECORE-BF) identifying individuals at high developing T2D prediabetes. Materials Methods: A cross-sectional was carried out involving 418,343 Spanish workers. fat percentage estimated using ECORE-BF equation, assessed validated models, including Finnish Diabetes Risk Score (FINDRISC), QDiabetes score (QD-score), others. The discriminatory power predicting receiver operating characteristic (ROC) curve analysis. Results: showed strong correlation high-risk classifications across all scales. area under ROC (AUC) exceeded 0.95 both men women, demonstrating accuracy. Conclusions: Adipose distribution, particularly visceral adiposity, is central factor dysfunction. provides cost-effective alternative large-scale assessment. Future research should explore impact reduction on prevention integration estimation scales into clinical public strategies.
Язык: Английский
Процитировано
0
Diabetology & Metabolic Syndrome, Год журнала: 2025, Номер 17(1)
Опубликована: Апрель 4, 2025
White adipose tissue (WAT) is highly flexible and was previously considered a passive location for energy storage. Its endocrine function has been established several years, earning it the title of an "endocrine organ" due to its ability secrete many adipokines that regulate metabolism. WAT one core tissues influence insulin sensitivity. dysfunction enhances resistance type 2 diabetes (T2D) progression. However, T2D may cause dysfunction, including changes in distribution, metabolism, adipocyte hypertrophy, inflammation, aging, free fatty acid levels, which exacerbate resistance. This review used PubMed search effects these on Additionally, we described discussed antidiabetic drugs, therapy, sulfonylureas, metformin, glucose-like peptide-1 receptor agonists, thiazolidinediones, sodium-dependent glucose transporters-2 inhibitors, parameters under conditions.
Язык: Английский
Процитировано
0
Assay and Drug Development Technologies, Год журнала: 2025, Номер unknown
Опубликована: Май 7, 2025
While sodium-glucose transporter 2 inhibitors (SGLT2i) demonstrate urate-lowering effects, their causal role in Gout prevention remains controversial. This study employs advanced Mendelian randomization (MR) techniques to dissect immune-mediated mechanisms underlying this relationship. Using bidirectional two-sample MR and mediation analysis, we analyzed genetic instrument variables for SGLT2i (10 single-nucleotide polymorphisms, F-statistic >20), risk (6,810 cases/477,788 controls), 731 immune cell phenotypes. Pleiotropy heterogeneity were also assessed ensure robustness. The confirmed a significant indirect effect of SGLT2i, which exhibited 2.6% reduced (Odds Ratio [OR]: 0.9738, 95% confidence interval [CI] = 0.9623, 0.9854, P 1.12e-05). Thirty-five phenotypes identified as significantly affecting development, with key such CD86 on myeloid Dendritic (DC) (OR: 0.9966; CI 0.9930, 0.9995), contributing 12.8% the overall effect. No evidence or pleiotropy was detected reverse-direction corroborated these findings. Our first established Gout-protective agents through DC-mediated immunomodulation, offering mechanistic insights targeted strategies clinical practice.
Язык: Английский
Процитировано
0
Life Sciences, Год журнала: 2023, Номер 335, С. 122285 - 122285
Опубликована: Ноя. 22, 2023
Язык: Английский
Процитировано
1
Microscopy Research and Technique, Год журнала: 2024, Номер 87(12), С. 2929 - 2942
Опубликована: Июль 25, 2024
Abstract Hypertension (HTN) is a prevalent chronic disease. HTN and liver disease association extensively noted. Thus, finding medication that can alleviate its accompanying insult would be promising. This study investigated the potential impacts of canagliflozin “sodium–glucose cotransporter‐2 inhibitor” on N ω ‐nitro‐L‐arginine methyl ester (L‐NAME)‐induced rat model. Twenty‐four adult male rats were divided into four groups; negative control group, L‐NAME group: 50 mg/kg was injected daily for 5 weeks + 1 week after injection both (40 mg/kg) given concomitantly further 4 weeks. Liver functions, serum lipid profile, hepatic oxidative/nitrative stress biomarkers, gene expression lipogenic enzymes, B‐cell lymphoma 2 (Bcl2), DNA fragmentation, measured. Besides, histology immunohistochemistry nuclear factor kappa B (NF‐κB) endothelial nitric oxide synthase (eNOS) assessed. Canagliflozin improved lipogenesis via downregulation fatty acid (FAS) transcriptional regulatory element binding protein 1c (SREBP1c) genes leading to an profile. Further, modified eNOS/inducible (iNOS) pathway decreased NF‐κB immunoreactivity besides restoring oxidants–antioxidants balance; increased reduced glutathione concomitant with declined malondialdehyde. improvement mirrored by significant restoration architecture confirmed preserved content upregulation antiapoptotic Bcl2 mRNA level attenuation alanine transaminase, aspartate aminotransferase. In conclusion, promising anti‐hypertensive hepatic‐supportive medication. Research Highlights Canagliflozin's antioxidant, anti‐inflammatory, anti‐lipogenic, characteristics mitigate remote compromise caused hypertension. exploited as hepatoprotective antihypertensive
Язык: Английский
Процитировано
0