Pflugers Archiv : European journal of physiology最新文献

{"title":"The obesity pandemic and its impact on non-communicable disease burden.","authors":"Staffan Hildebrand, Alexander Pfeifer","doi":"10.1007/s00424-025-03066-8","DOIUrl":"https://doi.org/10.1007/s00424-025-03066-8","url":null,"abstract":"<p><p>The rising prevalence of overweight and obesity across the globe is a major threat both to public health and economic development. This is mainly due to the link of obesity with the development and outcomes of non-communicable diseases (NCDs). NCDs are a leading cause of global death and disability, and reducing the burden of NCDs on patients and healthcare systems is of critical importance to improve public health. Obesity is projected to be the number one preventable risk factor for NCDs by 2035, and there is an urgent need to tackle the growing obesity rates in order to reduce NCD incidence and severity. Here, we review the current understanding of the impact of obesity on NCD burden in general, as well as the epidemiological and mechanistic relationship between obesity and some of the most common classes of NCDs. By literature review, we found that over 70% of NCDs have a documented association with obesity, highlighting the importance of a better understanding of the pathophysiologies underlying obesity/overweight as well as the interaction between obesity and NCDs in order to reduce global disease burden.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sphingosine kinase 1 inhibition aggravates vascular smooth muscle cell calcification.","authors":"Mehdi Razazian, Sheyda Bahiraii, Isratul Jannat, Adéla Tiffner, Georg Beilhack, Bodo Levkau, Jakob Voelkl, Ioana Alesutan","doi":"10.1007/s00424-025-03068-6","DOIUrl":"https://doi.org/10.1007/s00424-025-03068-6","url":null,"abstract":"<p><p>Medial vascular calcification is common in chronic kidney disease patients and linked to hyperphosphatemia. Upon phosphate exposure, intricate signaling events orchestrate pro-calcific effects in the vasculature mediated by vascular smooth muscle cells (VSMCs). Sphingosine kinase 1 (SPHK1) produces sphingosine-1-phosphate (S1P) and is associated with complex effects in the vascular system. The present study investigated a possible involvement of SPHK1 in VSMC calcification. Experiments were performed in primary human aortic VSMCs under pro-calcific conditions, with pharmacological inhibition or knockdown of SPHK1 or SPNS2 (a lysolipid transporter involved in cellular S1P export), as well as in Sphk1-deficient and wild-type mice treated with cholecalciferol. In VSMCs, SPHK1 expression was up-regulated by pro-calcific conditions. Calcification medium up-regulated osteogenic marker mRNA expression and activity as well as calcification of VSMCs, effects significantly augmented by co-treatment with the SPHK1 inhibitor SK1-IN-1. SK1-IN-1 alone was sufficient to up-regulate osteogenic signaling in VSMCs during control conditions. Similarly, the SPHK1 inhibitor PF-543 and SPHK1 knockdown up-regulated osteogenic signaling in VSMCs and aggravated VSMC calcification. In contrast, co-treatment with the SPNS2 inhibitor SLF1081851 suppressed osteogenic signaling and calcification of VSMCs, effects abolished by silencing of SPHK1. In addition, Sphk1 deficiency aggravated vascular calcification and aortic osteogenic marker expression in mice after cholecalciferol overload. In conclusion, SPHK1 inhibition, knockdown, or deficiency aggravates vascular pro-calcific signaling and calcification. The reduced calcification after inhibition of S1P export suggests a possible involvement of intracellular S1P, but further studies are required to elucidate the complex roles of SPHKs and S1P signaling in calcifying VSMCs.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancement of physiology via adaptive transcription.","authors":"Thomas Lissek","doi":"10.1007/s00424-024-03037-5","DOIUrl":"10.1007/s00424-024-03037-5","url":null,"abstract":"<p><p>The enhancement of complex physiological functions such as cognition and exercise performance in healthy individuals represents a challenging goal. Adaptive transcription programs that are naturally activated in animals to mediate cellular plasticity in response to stimulation can be leveraged to enhance physiological function above wild-type levels in young organisms and counteract complex functional decline in aging. In processes such as learning and memory and exercise-dependent muscle remodeling, a relatively small number of molecules such as certain stimulus-responsive transcription factors and immediate early genes coordinate widespread changes in cellular physiology. Adaptive transcription can be targeted by various methods including pharmaceutical compounds and gene transfer technologies. Important problems for leveraging adaptive transcription programs for physiological enhancement include a better understanding of their dynamical organization, more precise methods to influence the underlying molecular components, and the integration of adaptive transcription into multi-scale physiological enhancement concepts.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"187-199"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyperglucagonemia and glucagon hypersecretion in early type 2 diabetes result from multifaceted dysregulation of pancreatic mouse α-cells.","authors":"Antonia Ruiz-Pino, Arianna Goncalves-Ramírez, Margarita Jiménez-Palomares, Beatriz Merino, Manuel Castellano-Muñoz, Jean F Vettorazzi, Alex Rafacho, Laura Marroquí, Ángel Nadal, Paloma Alonso-Magdalena, Germán Perdomo, Irene Cózar-Castellano, Ivan Quesada","doi":"10.1007/s00424-024-03045-5","DOIUrl":"10.1007/s00424-024-03045-5","url":null,"abstract":"<p><p>Hyperglucagonemia has been implicated in the pathogenesis of type 2 diabetes (T2D). In contrast to β-cells, studies on the function of the pancreatic α-cell in T2D are scarce. Consequently, the processes underlying hyperglucagonemia and α-cell dysfunction are largely unknown, limiting the appropriate design of specific pharmacological and therapeutic strategies. In the current study, we aimed to analyze the alterations of the pancreatic α-cell and its glucagon responses in diabetic db/db mice at early stages of the disease. In this context of glucose intolerance, hyperinsulinemia, and β-cell dysfunction, hyperglucagonemia was only present at fed conditions and was associated with insulin resistance. Yet, we found that the glucagon-to-insulin ratio in db/db mice did not change with fed or fasted states, further supporting that the metabolic regulation of glucagon release was impaired. Pancreatic β-cell dysfunction in db/db mice was manifested by increased basal secretion from isolated islets along with reduced insulin content. In contrast, α-cells from diabetic animals presented upregulated secretion and islet content of glucagon compared with controls. Electrophysiological analysis of dispersed α-cells revealed that altered secretion was not the result of impaired exocytosis. Instead, we found defective regulation of Ca²⁺ signaling by glucose. Besides these functional alterations, we also observed augmented α-cell mass in diabetic mice, which was accompanied by disrupted islet cytoarchitecture as well as increased α-cell size and number, without pieces of evidence of upregulated proliferation. Overall, these findings indicate that hyperglucagonemia in early T2D results from multifaceted α-cell deregulation in mice.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"207-221"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142731788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic rose oxide and exercise synergistically modulate cardiovascular and autonomic functions in hypertensive rats.","authors":"Juliana A da Silva, Samuel S P Araújo, Ana Flávia M da Silva, José Guilherme V de Assunção, Pâmela de S Santos, José L Pereira Júnior, Carlos Eduardo S Dos Reis, Liana de M Santana, Regina G Silva, Ariell A de Oliveira, Francisca V S Nunes, Aldeidia P de Oliveira, Damião P de Sousa, Renato Nery Soriano, Luiz G S Branco, Helio C Salgado, João Paulo J Sabino","doi":"10.1007/s00424-024-03035-7","DOIUrl":"10.1007/s00424-024-03035-7","url":null,"abstract":"<p><p>With the alarming rise in cases of arterial hypertension worldwide, there is an urgent need to develop combined therapies to mitigate this scenario. Rose oxide (RO), a monoterpene with anti-inflammatory and hypotensive properties, emerges as an alternative. The present study is the first to evaluate the effect of RO administered chronically and combined with physical exercise (swimming) since both have been reported to have beneficial impacts on hypertension. Male SHR and Wistar rats (aged 12 weeks) received RO for 34 consecutive days (orally; 100 mg/kg). The progression of systolic arterial pressure (SAP) was monitored through tail-cuff plethysmography. Twenty-four hours before the end of the treatment, the animals were anesthetized, and the femoral artery and vein were cannulated to record the pulsatile arterial pressure and to administer drugs, respectively. Hemodynamic and autonomic parameters and baroreflex sensitivity and intrinsic heart rate (IHR) were evaluated. Treatment with RO, administered alone or combined with exercise, reduced SAP and mean arterial pressure in SHR. The swimming protocol did not prevent increases in BP, but when combined with RO, it improved autonomic control, assessed through heart rate variability and parasympathetic tone. IHR was attenuated in SHR, and none of the treatments reversed this response. Therefore, combining RO with physical exercise may enhance their antihypertensive effects, improving autonomic function, reducing oxidative stress and inflammation, providing synergistic cardiovascular benefits, improving metabolic health, promoting a comprehensive lifestyle intervention, and potentially allowing for reduced medication dosages. This multifaceted approach could offer a more effective and sustainable strategy for managing hypertension.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"241-251"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diet-induced impairment of skeletal muscle and adipose tissue metabolic homeostasis and its prevention by probiotic administration.","authors":"Angela Di Porzio, Valentina Barrella, Luisa Cigliano, Gianluigi Mauriello, Antonio Dario Troise, Andrea Scaloni, Susanna Iossa, Arianna Mazzoli","doi":"10.1007/s00424-024-03041-9","DOIUrl":"10.1007/s00424-024-03041-9","url":null,"abstract":"<p><p>Western dietary pattern is one of the main contributors to the increased risk of obesity and chronic diseases, through oxidative stress and inflammation, that are the two key mechanisms targeting metabolic organs, such as skeletal muscle and adipose tissue. The chronic exposure to high levels of dietary fatty acids can increase the amount of intramyocellular lipids in skeletal muscle, altering glucose homeostasis and contributing to a reduction in mitochondrial oxidative capacity. Probiotic administration is a promising approach as preventive strategy to attenuate metabolic damage induced by Western diet. Here, we investigated the beneficial effect of Limosillactobacillus reuteri DSM 17938 on the inflammatory state and oxidative balance in the skeletal muscle and adipose tissue of adult rats fed a western diet for 8 weeks, focusing on the role of skeletal muscle mitochondria. Limosillactobacillus reuteri DSM 17938 administration protected the skeletal muscle from mitochondrial dysfunction and oxidative stress, preventing the establishment of inflammation and insulin resistance. Interestingly, a further beneficial effect of the probiotic was exerted on body composition, favoring the deposition of protein mass and preventing adipose tissue hypertrophy and inflammation. These results open the possibility for the use of this probiotic in therapeutic approaches for nutrition-related diseases.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"223-239"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRPC3-mediated NFATc1 calcium signaling promotes triple negative breast cancer migration through regulating glypican-6 and focal adhesion.","authors":"Yan Wang, Xiaosheng Zhuang, Yanxiang Qi, Lung Yiu, Zhenping Li, Yuk Wah Chan, Xianji Liu, Suk Ying Tsang","doi":"10.1007/s00424-024-03030-y","DOIUrl":"10.1007/s00424-024-03030-y","url":null,"abstract":"<p><p>Canonical transient receptor potential isoform 3 (TRPC3), a calcium-permeable non-selective cation channel, has been reported to be upregulated in breast cancers and a modulator of cell migration. Calcium-sensitive transcription factor NFATc1, which is important for cell migration, was shown to be frequently activated in triple negative breast cancer (TNBC) biopsy tissues. However, whether TRPC3-mediated calcium influx would activate NFATc1 and affect the migration of TNBC cells, and, if yes, the underlying mechanisms involved, remain to be investigated. By immunostaining followed by confocal microscopy, TNBC lines MDA-MB-231 and BT-549 were both found to express TRPC3 on their plasma membrane while ER⁺ line MCF-7 and HER2⁺ line SK-BR3 do not. Blockade of TRPC3 by pharmacological inhibitor Pyr3 or stable knockdown of TRPC3 by lentiviral vector both inhibited cell migration as measured by wound healing assay. Importantly, blocking TRPC3 by Pyr3 or knockdown of TRPC3 both caused the translocation of NFATc1 from the nucleus to the cytosol as revealed by confocal microscopy. Interestingly, NFATc1 was found to bind to the promoter of glypican 6 (GPC6) as determined by chromatin immunoprecipitation assay. Consistently, knockdown of TRPC3 decreased the expression of GPC6 as revealed by western blotting. Moreover, long-term knockdown of GPC6 by lentiviral vector also consistently decreased the migration of TNBC cells. Intriguingly, GPC6 proteins physically interact with vinculin in MDA-MB-231 as determined by co-immunoprecipitation. Blockade of TRPC3, knockdown of TRPC3 or knockdown of GPC6 all induced larger, stabilized actin-bound peripheral focal adhesion (FA) formations in TNBC cells as determined by co-staining of actin and vinculin followed by confocal microscopy. These large, stabilized actin-bound peripheral FAs indicated a defective FA turnover, and were reported to be responsible for impairing directed cell migration. Our results suggest that, in TNBC cells, calcium influx through TRPC3 channel positively regulates NFATc1 nuclear translocation and GPC6 expression, which maintains the dynamics of FA turnover and optimal cell migration. Our study reveals a novel TRPC3-NFATc1-GPC6-vinculin signaling cascade in maintaining the migration of TNBC cells.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"253-272"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142472226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lessons from a model: early glucagon dysfunction in type 2 diabetes.","authors":"Shawn Duckett, Patrick E MacDonald","doi":"10.1007/s00424-024-03062-4","DOIUrl":"10.1007/s00424-024-03062-4","url":null,"abstract":"","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"201-203"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142953143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Like a Phoenix Reborn from the Ashes: TASK-5 - Commentary to Rinne & Schick et al.","authors":"Guiscard Seebohm","doi":"10.1007/s00424-024-03057-1","DOIUrl":"10.1007/s00424-024-03057-1","url":null,"abstract":"","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"205-206"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142953194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardioprotective effects of H3 receptor activation could be double-sided: insights from isoproterenol-induced cardiac injury.","authors":"H Fehmi Özel, Mustafa Özbek, Merve Temel Özden, H Seda Vatansever","doi":"10.1007/s00424-024-03039-3","DOIUrl":"10.1007/s00424-024-03039-3","url":null,"abstract":"<p><p>Histamine H3 receptors (H3Rs) are known to modulate neurotransmitter release in the nervous system, but their role in cardiac injury remains unclear. The present study aimed to investigate the cardioprotective role of H3Rs in a mouse model of myocardial injury. Forty BALB/c male mice were divided into four groups: Control (SF), Isoproterenol (ISO), Imetit (IMT), and IMT + ISO. The IMT and IMT + ISO groups were pretreated orally with 10 mg/kg imetit-dihydrobromide(imetit) for 7 days. In the last 2 days, the ISO and IMT + ISO groups received a subcutaneous injection of 85 mg/kg isoproterenol to induce myocardial ischemia. Electrocardiogram (ECG) recordings were obtained, and heart tissues were analyzed histopathologically. The results demonstrated that the administration of imetit resulted in the prolongation of the PR interval in the IMT group. QRS and QT intervals were prolonged in the ISO group. The J-wave area in the ISO group was significantly larger than in the other groups. Histopathological analyses revealed the presence of small vacuoles, inflammatory cell infiltration, and collagen aggregates in cardiomyocytes in the ISO group. No significant cellular changes were observed in the IMT group, in contrast. The IMT + ISO group exhibited fewer ischemic findings than the ISO group. Immunohistochemical analyses revealed positive H3R immunoreactivity in all groups. Imetit pretreatment increased the immunoreactivity of H3Rs in both the IMT and IMT + ISO groups. The findings of this study suggest that H3Rs may be present on the postsynaptic side in cardiac myocytes, in addition to adrenergic presynaptic nerve endings. Furthermore, imetit has been found to significantly reduce the effects of myocardial ischemia by activating H3Rs. The better characterization of the postsynaptic role of H3Rs offers potential for the development of new therapeutic strategies.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"291-301"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}