Lina Ding, Jingjing Xia, Hua Wang, Junyi Qian, Xiaodan Jin, Yang Yang, Jing Xia, Wenbin Shang, Ming Chen
{"title":"Berberine Improves Glucose and Lipid Metabolism in Obese Mice through the Reduction of IRE1/GSK-3β Axis-Mediated Inflammation.","authors":"Lina Ding, Jingjing Xia, Hua Wang, Junyi Qian, Xiaodan Jin, Yang Yang, Jing Xia, Wenbin Shang, Ming Chen","doi":"10.2174/0118715303319434241113161606","DOIUrl":"https://doi.org/10.2174/0118715303319434241113161606","url":null,"abstract":"<p><strong>Introduction: </strong>Berberine (BBR) has the characteristics of repressing hyperglycemia, obesity, and inflammation, as well as improving insulin resistance. However, the underlying mechanism remains to be fully understood. This study explores whether BBR regulates inositol requiring enzyme 1 (IRE1)/glycogen synthase kinase 3 beta (GSK-3β) axis to resist obesity-associated inflammation, thereby improving glucolipid metabolism disorders.</p><p><strong>Method: </strong>Mice were fed a high-fat diet and administrated with BBR, followed by measurement of weight change, biochemical indicators, as well as glucose and insulin tolerance. Insulin-resistant 3T3-L1 adipocyte models were established, and the model cells were treated with BBR and IRE1 inhibitors. Cell viability was detected by cell counting kit-8 assay. Inflammatory factor secretion and glucose consumption were measured via specific kits. Oil red O staining was used to observe lipid droplet formation, and protein expressions in the IRE1/GSK-3β axis were determined via Western blot.</p><p><strong>Results: </strong>BBR reduced weight, insulin resistance, levels of triglyceride, total cholesterol, free fatty acid, high-density lipoprotein, and low-density lipoprotein but improved glucose tolerance in obese mice. BBR and IRE1 inhibitors demonstrated no cytotoxicity. BBR and IRE1 inhibitors diminished secretion of tumor necrosis factor-alpha, interleukin-6, and monocyte chemoattractant protein 1, lipid droplet formation, and values of p-IRE1/IRE1 and p-GSK-3β/GSK-3β, but elevated glucose consumption in insulin-resistant adipocytes.</p><p><strong>Conclusion: </strong>BBR improves glucose and lipid metabolism in obese mice through the reduction of IRE1/GSK-3β axis-mediated inflammation, showing the great potential of BBR in reversing insulin resistance in obesity.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142960982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Improving Renal Protection in Chronic Kidney Disease Associated with Type 2 Diabetes: The Role of Finerenone.","authors":"Pringgodigdo Nugroho","doi":"10.2174/0118715303350851241021105850","DOIUrl":"https://doi.org/10.2174/0118715303350851241021105850","url":null,"abstract":"<p><p>Chronic kidney disease (CKD) is a major complication of type 2 diabetes mellitus (T2D), which often leads to diabetic kidney disease (DKD). Traditional therapies, including renin- angiotensin-aldosterone system inhibitors and sodium-glucose cotransporter-2 inhibitors, are effective in slowing CKD progression. However, these approaches are insufficient to comprehensively inhibit mineralocorticoid receptor (MR) overactivation in the kidneys, which remains a significant driver of inflammation, fibrosis, and oxidative stress. These pathological processes accelerate kidney damage and cardiovascular complications. Finerenone-a nonsteroidal mineralocorticoid receptor antagonist-represents a new frontier in renal protection. Unlike steroidal mineralocorticoid antagonists (MRAs), finerenone offers a more selective MR blockade, reducing kidney inflammation and fibrosis without significantly raising serum potassium levels. Landmark trials have demonstrated the ability of finerenone to significantly reduce kidney and cardiovascular events in patients with T2D and CKD. Clinical evidence has highlighted finerenone as an effective option for slowing DKD progression while maintaining a favorable safety profile. Based on these findings, recent guidelines have incorporated finerenone as a recommended therapy for patients with T2D and CKD, emphasizing its role in reducing both renal and cardiovascular risks. This review provides a comprehensive overview of the available data to offer a deeper understanding of the potential of finerenone to transform CKD management for T2D patients.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Significance of Serum Magnesium in Parathyroid Hormone Level in Patients with Chronic Kidney Disease.","authors":"Jiali Wang, Yongda Lin, Xiutian Chen, Hong-Yan Li, Wenzhuang Tang, Tianbiao Zhou","doi":"10.2174/0118715303311081241022042321","DOIUrl":"https://doi.org/10.2174/0118715303311081241022042321","url":null,"abstract":"<p><strong>Introduction: </strong>In chronic kidney disease (CKD) patients, elevated parathyroid hormone (PTH) is linked to cardiovascular mortality and morbidity. Levels of PTH are influenced by serum phosphate (P) and calcium (Ca), but little is known about the impact of magnesium (Mg) on PTH. Hence, this study investigated the relationship between PTH and Mg in peritoneal dialysis (PD) patients and non-dialysis patients from three hospitals in China.</p><p><strong>Material and methods: </strong>This cross-sectional study included 446 chronic kidney disease stage 5 (CKD5) patients from three hospitals in southern China. PTH was naturally transformed to Ln_PTH for analysis. The chi-square test, Pearson correlation analysis, hierarchical regression analysis, and t-test were used to explore the relationships between Ln_PTH and gender, diabetes history, Mg, P, Ca, albumin (Alb), red blood cells (RBC), hemoglobin (Hb), white blood cells (WBC), and platelet (Plt).</p><p><strong>Results: </strong>Patients with diabetes mellitus (DM) had lower levels of Ln_PTH in PD (P<0.05) and non-dialysis (P>0.05) patients. Ln_PTH levels were negatively associated with Mg and Ca but positively associated with P and Alb in PD patients (all P<0.05). Ln_PTH levels were negatively associated with age but positively associated with P in non-dialysis patients (all P<0.05).</p><p><strong>Conclusion: </strong>This study demonstrates the negative effect of Mg and diabetes on Ln_PTH levels in CKD5 patients.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Do SGLT2 Inhibitors Protect the Kidneys? An Alternative Explanation.","authors":"Jacob Ilany","doi":"10.2174/0118715303355221241021050443","DOIUrl":"https://doi.org/10.2174/0118715303355221241021050443","url":null,"abstract":"<p><p>SGLT2 inhibitors are a family of drugs that were developed to treat diabetes mellitus. In randomized controlled trials, SGLT2 inhibitors seem to prevent kidney deterioration in patients with nephropathies, both diabetic and non-diabetic. However, in contrast to biochemical/physiological results (proteinuria and serum creatinine levels) that improve in all studies, the clinical results (all-cause mortality, cardiovascular death, need for dialysis, or renal transplant) do not consistently improve. In this article, the author would like to suggest that SGLT2 inhibitors do not, in fact, prevent the progression of renal diseases but rather alter laboratory results. This study will present a theory that gives an alternative explanation for the findings in the studies that would explain the above discrepancy between biochemical/physiological and clinical results. In general, the author claims that SGLT2 inhibitors change the kinetics of renal creatinine and microalbumin excretion but do not prevent parenchymal adverse changes in kidneys. This causes a dissociation between renal function markers (such as serum creatinine level and urinary protein) and the real kidney function. Thus, the clinical renal prognosis does not improve despite seemingly better laboratory results.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Liu Muge, Xiao Xiongsheng, Jin Ling, Li Siyi, Zheng Changwei, Chen Zhengde, Chen Zhuoting, Zhi Zhang
{"title":"Evaluating the Relationship between Cathepsins and Papillary Thyroid Carcinoma: A Mendelian Randomization Study.","authors":"Liu Muge, Xiao Xiongsheng, Jin Ling, Li Siyi, Zheng Changwei, Chen Zhengde, Chen Zhuoting, Zhi Zhang","doi":"10.2174/0118715303305715240912172648","DOIUrl":"https://doi.org/10.2174/0118715303305715240912172648","url":null,"abstract":"<p><strong>Background: </strong>Papillary Thyroid Carcinoma (PTC) is the most common thyroid cancer, with an etiology and progression that are not fully understood. Research suggests a link between cathepsins and PTC, but the causal nature of this link is unclear. This study uses Mendelian Randomization (MR) to investigate if cathepsins causally influence PTC risk.</p><p><strong>Methods: </strong>We applied univariable and multivariable MR analyses using genetic variants as proxies for cathepsin levels. Genetic data for cathepsins were sourced from the INTERVAL study, while PTC data came from the Finnish Genome-Wide Association Study database. Our analysis employed several MR methods, including the Inverse Variance Weighted (IVW) approach, MR-Egger, and the Weighted Median method, to provide comprehensive insights and address possible pleiotropy.</p><p><strong>Results: </strong>MR findings suggest a significant causal association between higher cathepsin levels and increased PTC risk. Notably, genetic variants indicating higher cathepsin Z expression were positively causal associated with PTC risk (OR:1.1190, 95% CI: 1.0029-1.2486), multivariable analysis confirmed significant carcinogenesis role of cathepsin Z in PTC (OR: 1.1593, 95% CI: 1.0137-1.3258), with results consistent across various tests, indicating a robust relationship.</p><p><strong>Conclusion: </strong>This study established a causal link between cathepsin levels and PTC risk, emphasizing the roles of cathepsin Z in its progression. These insights could lead to new therapeutic strategies targeting these enzymes. Further research is necessary to understand the underlying biological mechanisms and their clinical implications.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Case Report of Recurrent Primary Pituitary Abscess: Challenges in Diagnosis and Treatment.","authors":"Dilan Ozaydin, Ahmet Numan Demir, Tufan Agah Kartum, Ender Vergili, Pinar Kadioglu, Necmettin Tanriover","doi":"10.2174/0118715303338996241021094336","DOIUrl":"https://doi.org/10.2174/0118715303338996241021094336","url":null,"abstract":"<p><strong>Background: </strong>Primary pituitary abscess is a rare disease with no specific symptoms for pituitary abscess alone. A preoperative diagnosis is quite challenging due to unclear imaging findings.</p><p><strong>Case presentation: </strong>We report the case of a patient with a pituitary lesion who presented with hypopituitarism, diabetes insipidus, and visual field defect and was misdiagnosed as a possible cystic pituitary adenoma. Endoscopic endonasal transsphenoidal surgery (ETSS) was performed, and surprisingly, only pus was found, and complete resection of the lesion was achieved. Coagulase-negative staphylococci were detected in the culture, and appropriate antibiotic therapy was administered for six weeks. Diabetes insipidus and hypopituitarism did not improve. One year later, the abscess recurred, and a second operation with complete resection was performed.</p><p><strong>Conclusion: </strong>Knowledge of primary pituitary abscess, a rare infectious disease, is essential for early detection and successful treatment. Most patients have a chronic and silent prediagnostic course with symptoms that are not specific to pituitary abscess alone. The primary treatment option is EETS, followed by long-term, relevant antibiotics. The disease can be resistant and recur despite appropriate treatment, especially in patients with risk factors. Therefore, long-term follow-up of patients is essential.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Gut Microbiota and Diabetes: Pioneering New Treatment Frontiers.","authors":"Rupendra Shakya, Ponnurengam Malliappan Sivakumar, Pranav Kumar Prabhakar","doi":"10.2174/0118715303342579241119155225","DOIUrl":"https://doi.org/10.2174/0118715303342579241119155225","url":null,"abstract":"<p><p>Diabetes Mellitus (DM) is a complex metabolic disorder characterized by chronic hyperglycemia and poses significant global health challenges. Conventional treatments, such as insulin therapy and lifestyle modifications, have shown limited efficacy in addressing the multifactorial nature of DM. Emerging evidence suggests that gut microbiota, a diverse community of microorganisms critical for metabolism and immune function, plays a pivotal role in metabolic health. Dysbiosis, an imbalance in gut microbiota composition, has been linked to insulin resistance, obesity, and DM. Gut microbiota influences glucose metabolism through mechanisms, including short-chain fatty acid production, gut permeability regulation, and immune system interactions, indicating a bidirectional relationship between microbial health and metabolism. Clinical and experimental studies demonstrate that modulating gut microbiota through dietary interventions (prebiotics, probiotics, synbiotics) improves glycemic control and insulin sensitivity in DM patients. Fecal Microbiota Transplantation (FMT) has also shown promise in restoring healthy gut microbiota and alleviating DM-related metabolic disturbances. However, challenges remain, including the need for personalized treatments due to individual microbiota variability and the unknown long-term effects of these interventions. Future research should focus on elucidating the mechanisms by which gut microbiota influences metabolism and refining personalized approaches to enhance DM management.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yancheng Huo, Meng Guo, Yihan Li, Xingchen Yao, Qingxian Tian, Tie Liu
{"title":"Identification of Programmed Cell Death-related Biomarkers for the Potential Diagnosis and Treatment of Osteoporosis.","authors":"Yancheng Huo, Meng Guo, Yihan Li, Xingchen Yao, Qingxian Tian, Tie Liu","doi":"10.2174/0118715303326112241021061805","DOIUrl":"https://doi.org/10.2174/0118715303326112241021061805","url":null,"abstract":"<p><strong>Background: </strong>Osteoporosis (OP) is a skeletal condition characterized by increased susceptibility to fractures. Programmed cell death (PCD) is the orderly process of cells ending their own life that has not been thoroughly explored in relation to OP.</p><p><strong>Objective: </strong>This study is to investigate PCD-related genes in OP, shedding light on potential mechanisms underlying the disease.</p><p><strong>Methods: </strong>Public datasets (GSE56814 and GSE56815) were analyzed to identify differentially expressed genes (DEGs). We employed the least absolute shrinkage and selection operator (LASSO), Boruta, and random forest (RF) algorithms to pinpoint hub PCD-related genes in OP and construct a predictive nomogram model. The performance of the model was validated through ROC curve analysis, calibration curves, and decision curve analysis. Additionally, transcription factor (TF) interaction analysis and functional enrichment analysis were conducted to explore the regulatory networks and biological pathways involved.</p><p><strong>Results: </strong>We identified 161 DEGs, with 30 prominently associated with PCD. Five hub genes, PDPK1, MAP1LC3B, ZFP36, DRAM1, and MPO, were highlighted as particularly significant. A predictive nomogram integrating these genes demonstrated high accuracy (AUC) in forecasting OP risk, with an AUC of 0.911 in the GSE56815 dataset. The validation confirmed the gene model efficacy in differentiating OP risk and clinical applicability. The subsequent TF-gene interaction analyses revealed that these hub genes are regulated by multiple TFs, indicating their central role in OP pathology. Functional enrichment analysis of the hub genes indicated significant involvement in apoptosis, autophagy, and immune response pathways.</p><p><strong>Conclusion: </strong>This study identified PDPK1, MAP1LC3B, ZFP36, DRAM1, and MPO as potential biomarkers and proposes a nomogram based on hub genes for predicting osteoporosis risk.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Identification of Biomarkers Related to Liquid-Liquid Phase Separation for Ulcerative Colitis Based on Single-Cell and Bulk RNA Transcriptome Sequencing Data.","authors":"Jicheng Lu, Xu Lu, Bin Chen","doi":"10.2174/0118715303355042241208171133","DOIUrl":"https://doi.org/10.2174/0118715303355042241208171133","url":null,"abstract":"<p><strong>Background: </strong>Liquid-Liquid Phase Separation (LLPS) is a process involved in the formation of established organelles and various condensates that lack membranes; however, the relationship between LLPS and Ulcerative Colitis (UC) remains unclear.</p><p><strong>Aims: </strong>This study aimed to comprehensively clarify the correlation between ulcerative colitis (UC) and liquid-liquid phase separation (LLPS).</p><p><strong>Objectives: </strong>In this study, bioinformatics analyses and public databases were applied to screen and validate key genes associated with LLPS in UC. Furthermore, the roles of these key genes in UC were comprehensively analyzed.</p><p><strong>Methods: </strong>Based on the single-cell transcriptomic data of UC obtained from the Gene Expression Omnibus (GEO) database, differences between patients with UC and their controls were compared using the limma package. The single-cell data were then filtered and normalized by the 'Seurat' package and subjected to dimension reduction by the Uniform Manifold Approximation and Projection (UMAP) algorithm. The LLPS-related genes (LLPSRGs) were searched on the Dr- LLPS website to obtain cross-correlated genes, which were scored using the ssGSEA algorithm. Next, functional enrichment, interaction network, immune landscape, and diagnostic and drug prediction of the LLPSRGs were comprehensively explored. Finally, the results were validated using external datasets and quantitative real-time PCR (qRT-PCR).</p><p><strong>Results: </strong>A total of eight cell types in UC were classified, namely, fibroblasts, macrophages, endothelial cells, neutrophils, NK cells, B cells, epithelial cells, and T cells. The intersection between differently expressed genes (DEGs) among the eight cell types identified 44 key genes, which were predominantly enriched in immune- and infection-related pathways. According to receiver operating characteristic (ROC) curves, PLA2G2A, GZMK, CD69, HSP90B1, and S100A11 reached an AUC value of 0.94, 0.95, 0.86, 0.89, and 0.93, respectively. Drug prediction revealed that decitabine, tetrachlorodibenzodioxin, tetradecanoylphorbol acetate, thapsigargin, and cisplatin were the potential small molecular compounds for PLA2G2A, GZMK, CD69, HSP90B1, and S100A11. Immune cell infiltration analysis demonstrated that the infiltration of CD4 memory T cell activation, macrophage M1, T macrophage M0, neutrophils, and mast cell activation was higher in the UC group than in the normal group.</p><p><strong>Conclusion: </strong>The LLPSRGs play crucial roles in UC and can be used as prognostic and diagnostic markers for UC. The current findings contribute to the management of UC.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shruthi Rai P, Yashodhar P Bhandary, Shivarajashankara Ym, Akarsha B, Roopa Bhandary, Prajna Rh, Namrata Kg, Savin Cg, Priya Alva, P Katyayani, Sukanya Shetty, Sudhakar Tj
{"title":"Interlinking the Cross Talk on Branched Chain Amino Acids, Water Soluble Vitamins and Adipokines in the Type 2 Diabetes Mellitus Etiology.","authors":"Shruthi Rai P, Yashodhar P Bhandary, Shivarajashankara Ym, Akarsha B, Roopa Bhandary, Prajna Rh, Namrata Kg, Savin Cg, Priya Alva, P Katyayani, Sukanya Shetty, Sudhakar Tj","doi":"10.2174/0118715303305579241014112730","DOIUrl":"https://doi.org/10.2174/0118715303305579241014112730","url":null,"abstract":"<p><p>Type 2 Diabetes Mellitus (T2DM) is an etiologically diverse metabolic dysfunction that, if untreated, leads to chronic hyperglycemia. Understanding the etiology of T2DM is critical, as it represents one of the most formidable medical challenges of the twenty-first century. Traditionally, insulin resistance has been recognized as the primary risk factor and a well-known consequence of type 2 diabetes. Emerging evidence suggests that branched-chain amino acids (BCAAs), adipokines, and deficiencies in water-soluble vitamins, such as thiamine and pyridoxine, play significant roles in the development of insulin resistance, a key feature of T2DM. These factors are interconnected through the AMP-activated protein kinase (AMPK) pathway, which regulates various metabolic processes, including glucose transport, lipid synthesis, and inflammatory responses. Dysregulation of AMPK is linked to insulin resistance and metabolic syndrome-related illnesses. Understanding the interplay between BCAAs, adipokines, vitamins, and AMPK may offer new therapeutic targets for the prevention and treatment of diabetes mellitus.</p>","PeriodicalId":94316,"journal":{"name":"Endocrine, metabolic & immune disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}