Acta Physiologica最新文献

{"title":"Rapid stimulation of protein synthesis in digesting snakes: Unveiling a novel gut-pancreas-muscle axis","authors":"Emil Rindom,&nbsp;Katja Bundgaard Last,&nbsp;Anja Svane,&nbsp;Asger Fammé,&nbsp;Per G. Henriksen,&nbsp;Jean Farup,&nbsp;Niels Jessen,&nbsp;Frank Vincenzo de Paoli,&nbsp;Tobias Wang","doi":"10.1111/apha.70006","DOIUrl":"10.1111/apha.70006","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Snakes exhibit remarkable physiological shifts when their large meals induce robust postprandial growth after prolonged fasting. To understand the regulatory mechanisms underlying this rapid metabolic transition, we examined the regulation of protein synthesis in pythons, focusing on processes driving early postprandial tissue remodeling and growth.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using the SUnSET method with puromycin labeling, we measured in vivo protein synthesis in fasting and digesting snakes at multiple post-feeding intervals. Pyloric ligation, pancreatectomy, and plasma transfusions were performed to explore the roles of gastrointestinal luminal signaling and pancreatic function across key tissues.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We observed profound and early stimulation of protein synthesis in gastrointestinal tissues and skeletal muscle already 3 h after ingestion, before any measurable rise in plasma amino acids from the meal. The gastrointestinal stimulation appears to be driven by luminal factors, while the stimulation of skeletal muscle protein synthesis is humoral with pancreatic insulin release as an integral mediator. The pre-absorptive anabolic activity is supported by the release of amino acids from the breakdown of endogenous proteins.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings suggest that snakes initiate protein synthesis via distinct, tissue-specific pathways preceding nutrient absorption. This “pay before pumping” model shows how early protein synthesis prepares the digestive and muscular systems for later nutrient assimilation and growth. This intricate humoral regulation, involving a gut-pancreas-muscle axis, governs postprandial protein synthesis in snakes and provides insights into fundamental mechanisms driving metabolic adaptations and broader hyperplastic and hypertrophic responses.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The neonate respiratory microbiome","authors":"Sabine Pirr,&nbsp;Maike Willers,&nbsp;Dorothee Viemann","doi":"10.1111/apha.14266","DOIUrl":"10.1111/apha.14266","url":null,"abstract":"<p>Over the past two decades, it has become clear that against earlier assumptions, the respiratory tract is regularly populated by a variety of microbiota even down to the lowest parts of the lungs. New methods and technologies revealed distinct microbiome compositions and developmental trajectories in the differing parts of the respiratory tract of neonates and infants. In this review, we describe the current understanding of respiratory microbiota development in human neonates and highlight multiple factors that have been identified to impact human respiratory microbiome development including gestational age, mode of delivery, diet, antibiotic treatment, and early infections. Moreover, we discuss to date revealed respiratory microbiome–disease associations in infants and children that may indicate a potentially imprinting cross talk between microbial communities and the host immune system in the respiratory tract. It becomes obvious how insufficient our knowledge still is regarding the exact mechanisms underlying such cross talk in humans. Lastly, we highlight strong findings that emphasize the important role of the gut–lung axis in educating and driving pulmonary immunity. Further research is needed to better understand the host – respiratory microbiome interaction in order to enable the translation into microbiome-based strategies to protect and improve human respiratory health from early childhood.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potassium intake to regulate sodium excretion? Don't forget the anion","authors":"Matthew A. Bailey","doi":"10.1111/apha.14260","DOIUrl":"10.1111/apha.14260","url":null,"abstract":"&lt;p&gt;In the context of cardiovascular health, potassium has long been the forgotten cation, overshadowed by sodium occupying the “superior” position in the alkali metal series, Group 1 of the periodic table of elements. Epidemiological and interventional clinical trials are beginning to shift the dial, revealing health benefits of diets rich in potassium. The physiological mechanisms are not fully resolved. In this issue of &lt;i&gt;Acta Physiologica&lt;/i&gt; a study by Vitzhum and colleagues shows that increasing dietary potassium intake in mice reduces the sensitivity of the distal nephron to the sodium-retaining hormone aldosterone. Intriguingly, the accompanying anion may be the critical factor.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;The adverse health impact of high salt (NaCl) intake has long been recognized and dominates discourse related to modern dietary practice.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Many countries have public health policies with aspirations to reduce salt intake. Dietary potassium does not garner the same attention, despite estimates that daily intake is habitually below the ~100 mmoles/day threshold of adequacy.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; Indeed, when potassium is mentioned at all, it is common to caution against dietary overload and the risk of hyperkalemia in people with kidney disease, or those taking mineralocorticoid receptor (MR) antagonists and renin-angiotensin system blockers.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;The story is changing. Observational evidence associates higher potassium with reduced cardiovascular events, reduced mortality and lower albuminuria.&lt;span&gt;&lt;sup&gt;5-7&lt;/sup&gt;&lt;/span&gt; Recent interventional studies show that substitution of regular table salt (100% NaCl) with “low-salt” (75% NaCl and 25% KCl) lowers blood pressure and reduces cardiovascular events; benefits that seem to reflect an increase in potassium intake rather than the reduction in salt intake.&lt;span&gt;&lt;sup&gt;8, 9&lt;/sup&gt;&lt;/span&gt; Indeed, a meta-analysis of randomized controlled trials finds that oral potassium supplements reduces systolic blood pressure by ~3 mmHg, an effect size similar to that of monotherapy with front-line antihypertensive drugs.&lt;span&gt;&lt;sup&gt;10&lt;/sup&gt;&lt;/span&gt; The physiological mechanisms underpinning such benefits are not well understood. One possibility is that a potassium-rich diet facilitates sodium excretion by the kidneys. Indeed, the diuretic properties of oral potassium salts have long been recognized and the effect of potassium intake on kidney sodium transporter function has been a subject of intense research in the last decade. For example, NCC is the sodium chloride cotransporter in the apical membrane of the distal convoluted tubule and the target of thiazide diuretics.&lt;span&gt;&lt;sup&gt;11&lt;/sup&gt;&lt;/span&gt; It is now widely accepted that provision of oral potassium deactivates NCC.&lt;span&gt;&lt;sup&gt;11, 12&lt;/sup&gt;&lt;/span&gt; The intracellular mechanism is delineated: elevated extracellular potassium increases intracellular chloride concentration, directly inhibiting the kinase WNK","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14260","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DECORIN, a triceps-derived myokine, protects sorted β-cells and human islets against chronic inflammation associated with type 2 diabetes","authors":"Allan Langlois,&nbsp;Julien Cherfan,&nbsp;Emmanuelle Meugnier,&nbsp;Ahmad Rida,&nbsp;Caroline Arous,&nbsp;Claude Peronet,&nbsp;Harzo Hamdard,&nbsp;Bader Zarrouki,&nbsp;Bernhard Wehrle-Haller,&nbsp;Michel Pinget,&nbsp;Siobhan M. Craige,&nbsp;Karim Bouzakri","doi":"10.1111/apha.14267","DOIUrl":"10.1111/apha.14267","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Pancreatic β-cells are susceptible to inflammation, leading to decreased insulin production/secretion and cell death. Previously, we have identified a novel triceps-derived myokine, DECORIN, which plays a pivotal role in skeletal muscle-to-pancreas interorgan communication. However, whether DECORIN can directly impact β-cell function and susceptibility to inflammation remains unexplored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The effect of DECORIN was assessed in sorted human and rat β-cell and human islets from healthy and type 2 diabetes (T2D) donors. We assessed glucose-stimulated insulin secretion (GSIS) and cytokine-mediated cell death. We then challenged sorted β-cells and human islets with inflammatory cytokines commonly associated with diabetes, such as tumor necrosis factor-α (TNF-α) alone or in combination with interleukin1-β (IL1-β) and interferon-γ (cytomix).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>DECORIN enhanced cell spreading and the localization of phosphorylated FAK at adhesions, promoting GSIS under basal conditions. It also increased insulin granule docking adhesion length and countered the inhibitory effects of TNF-α on adhesion and actin remodeling at the β-cell surface, resulting in preserved GSIS. DECORIN protected from cell death in sorted β-cells and islets challenged with TNF-α alone or TNF-α + cytomix. Interestingly, DECORIN increased both insulin content and secretion in human islets from T2D individuals. Additionally, DECORIN treatment reversed the impaired gene expression caused by T2D and enhanced the expression of genes essential for islet function and metabolism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Collectively, we have shown that DECORIN had a beneficial effect on human islets, protecting them from inflammation-induced cell death. In T2D islets, DECORIN restores islet function and reverses the expression of T2D-associated genes. Based on our data, we propose that DECORIN is a promising therapeutic target for diabetes-associated inflammation and diabetes itself.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unfolded protein response: An essential element of intestinal homeostasis and a potential therapeutic target for inflammatory bowel disease","authors":"Miriam Di Mattia,&nbsp;Michele Sallese,&nbsp;Loris Riccardo Lopetuso","doi":"10.1111/apha.14284","DOIUrl":"10.1111/apha.14284","url":null,"abstract":"<p>Different physiological and pathological situations can produce alterations in the cell's endoplasmic reticulum (ER), leading to a condition known as ER stress, which can trigger an intricate intracellular signal transduction system known as the unfolded protein response (UPR). UPR is primarily tailored to restore proteostasis and ER equilibrium; otherwise, if ER stress persists, it can cause programmed cell death as a cytoprotective mechanism and drive inflammatory processes. Therefore, since intestinal cells strongly rely on UPR for their biological functions and unbalanced UPR has been linked to inflammatory, metabolic, and immune disorders, here we discussed the role of the UPR within the intestinal tract, focusing on the UPR contribution to inflammatory bowel disease development. Importantly, we also highlighted the promising potential of UPR components as therapeutic targets for intestinal inflammatory diseases.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ion permeability profiles of renal paracellular channel-forming claudins","authors":"Ioanna Pouyiourou,&nbsp;Anja Fromm,&nbsp;Jörg Piontek,&nbsp;Rita Rosenthal,&nbsp;Mikio Furuse,&nbsp;Dorothee Günzel","doi":"10.1111/apha.14264","DOIUrl":"10.1111/apha.14264","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Members of the claudin protein family are the major constituents of tight junction strands and determine the permeability properties of the paracellular pathway. In the kidney, each nephron segment expresses a distinct subset of claudins that form either barriers against paracellular solute transport or charge- and size-selective paracellular channels. It was the aim of the present study to determine and compare the permeation properties of these renal paracellular ion channel-forming claudins.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>MDCK II cells, in which the five major claudins had been knocked out (claudin quintupleKO), were stably transfected with individual mouse Cldn2, -4, -8, -10a, -10b, or -15, or with dog Cldn16 or -19, or with a combination of mouse Cldn4 and Cldn8, or dog Cldn16 and Cldn19. Permeation properties were investigated in the Ussing chamber and claudin interactions by FRET assays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Claudin-4 and -19 formed barriers against solute permeation. However, at low pH values and in the absence of HCO₃⁻, claudin-4 conveyed a weak chloride and nitrate permeability. Claudin-8 needed claudin-4 for assembly into TJ strands and abolished this anion preference. Claudin-2, -10a, -10b, -15, -16+19 formed highly permeable channels with distinctive permeation profiles for different monovalent and divalent anions or cations, but barriers against the permeation of ions of opposite charge and of the paracellular tracer fluorescein.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Paracellular ion permeabilities along the nephron are strictly determined by claudin expression patterns. Paracellular channel-forming claudins are specific for certain ions and thus lower transepithelial resistance, yet form barriers against the transport of other solutes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arrhythmogenic calmodulin variants D131E and Q135P disrupt interaction with the L-type voltage-gated Ca2+ channel (Cav1.2) and reduce Ca2+-dependent inactivation","authors":"Nitika Gupta,&nbsp;Ella M. B. Richards,&nbsp;Vanessa S. Morris,&nbsp;Rachael Morris,&nbsp;Kirsty Wadmore,&nbsp;Marie Held,&nbsp;Liam McCormick,&nbsp;Ohm Prakash,&nbsp;Caroline Dart,&nbsp;Nordine Helassa","doi":"10.1111/apha.14276","DOIUrl":"10.1111/apha.14276","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Long QT syndrome (LQTS) and catecholaminergic polymorphism ventricular tachycardia (CPVT) are inherited cardiac disorders often caused by mutations in ion channels. These arrhythmia syndromes have recently been associated with calmodulin (CaM) variants. Here, we investigate the impact of the arrhythmogenic variants D131E and Q135P on CaM's structure–function relationship. Our study focuses on the L-type calcium channel Ca_v1.2, a crucial component of the ventricular action potential and excitation–contraction coupling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used circular dichroism (CD), ¹H-¹⁵N HSQC NMR, and trypsin digestion to determine the structural and stability properties of CaM variants. The affinity of CaM for Ca²⁺ and interaction of Ca²⁺/CaM with Ca_v1.2 (IQ and NSCaTE domains) were investigated using intrinsic tyrosine fluorescence and isothermal titration calorimetry (ITC), respectively. The effect of CaM variants of Ca_v1.2 activity was determined using HEK293-Ca_v1.2 cells (B'SYS) and whole-cell patch-clamp electrophysiology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Using a combination of protein biophysics and structural biology, we show that the disease-associated mutations D131E and Q135P mutations alter apo/CaM structure and stability. In the Ca²⁺-bound state, D131E and Q135P exhibited reduced Ca²⁺ binding affinity, significant structural changes, and altered interaction with Ca_v1.2 domains (increased affinity for Ca_v1.2-IQ and decreased affinity for Ca_v1.2-NSCaTE). We show that the mutations dramatically impair Ca²⁺-dependent inactivation (CDI) of Ca_v1.2, which would contribute to abnormal Ca²⁺ influx, leading to disrupted Ca²⁺ handling, characteristic of cardiac arrhythmia syndromes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings provide insights into the molecular mechanisms behind arrhythmia caused by calmodulin mutations, contributing to our understanding of cardiac syndromes at a molecular and cellular level.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Left atrial reservoir strain as a predictor of cardiac dysfunction in a murine model of pressure overload","authors":"John P. Salvas,&nbsp;Thomas Moore-Morris,&nbsp;Craig J. Goergen,&nbsp;Pierre Sicard","doi":"10.1111/apha.14277","DOIUrl":"10.1111/apha.14277","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Left atrial (LA) strain is emerging as a valuable metric for evaluating cardiac function, particularly under pathological conditions such as pressure overload. This preclinical study investigates the predictive utility of LA strain on cardiac function in a murine model subjected to pressure overload, mimicking pathologies such as hypertension and aortic stenosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>High-resolution ultrasound was performed in a cohort of mice (<i>n</i> = 16) to evaluate left atrial and left ventricular function at baseline and 2 and 4 weeks after transverse aortic constriction (TAC). Acute adaptations in cardiac function were assessed in a subgroup of mice (<i>n</i> = 10) with 3 days post-TAC imaging.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We report an increase in LA max volume from 11.0 ± 4.3 μL at baseline to 26.7 ± 16.7 μL at 4 weeks (<i>p</i> = 0.002) and a decrease in LA reservoir strain from 20.8 ± 5.4% at baseline to 10.2 ± 6.9% at 4 weeks (<i>p</i> = 0.001). In the acute phase, LA strain dysfunction was present at 3 days (<i>p</i> &lt; 0.001), prior to alterations in LA volume (<i>p</i> = 0.856) or left ventricular (LV) ejection fraction (<i>p</i> = 0.120). LA reservoir strain correlated with key indicators of cardiac performance including left ventricular (LV) ejection fraction (<i>r</i> = 0.541, <i>p</i> &lt; 0.001), longitudinal strain (<i>r</i> = −0.637, <i>p</i> &lt; 0.001), and strain rate (<i>r</i> = 0.378, <i>p</i> = 0.007). Furthermore, markers of atrial structure and function including LA max volume (AUC = 0.813, <i>p =</i> 0.003), ejection fraction (AUC = 0.853, <i>p</i> = 0.001), and strain (AUC = 0.884, <i>p</i> &lt; 0.001) all predicted LV dysfunction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>LA strain and function assessments provide a reliable, non-invasive method for the early detection and prediction of cardiac dysfunction in a model of pressure overload.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phosphoproteomics for studying signaling pathways evoked by hormones of the renin-angiotensin system: A source of untapped potential","authors":"Igor Maciel Souza-Silva,&nbsp;Victor Corasolla Carregari,&nbsp;U. Muscha Steckelings,&nbsp;Thiago Verano-Braga","doi":"10.1111/apha.14280","DOIUrl":"10.1111/apha.14280","url":null,"abstract":"<p>The Renin-Angiotensin System (RAS) is a complex neuroendocrine system consisting of a single precursor protein, angiotensinogen (AGT), which is processed into various peptide hormones, including the angiotensins [Ang I, Ang II, Ang III, Ang IV, Ang-(1–9), Ang-(1–7), Ang-(1–5), etc] and Alamandine-related peptides [Ang A, Alamandine, Ala-(1–5)], through intricate enzymatic pathways. Functionally, the RAS is divided into two axes with opposing effects: the classical axis, primarily consisting of Ang II acting through the AT₁ receptor (AT₁R), and in contrast the protective axis, which includes the receptors Mas, AT₂R and MrgD and their respective ligands. A key area of RAS research is to gain a better understanding how signaling cascades elicited by these receptors lead to either “classical” or “protective” effects, as imbalances between the two axes can contribute to disease. On the other hand, therapeutic benefits can be achieved by selectively activating protective receptors and their associated signaling pathways. Traditionally, robust “hypothesis-driven” methods like Western blotting have built a solid knowledge foundation on RAS signaling. In this review, we introduce untargeted mass spectrometry-based phosphoproteomics, a “hypothesis-generating approach”, to explore RAS signaling pathways. This technology enables the unbiased discovery of phosphorylation events, offering insights into previously unknown signaling mechanisms. We review the existing studies which used phosphoproteomics to study RAS signaling and discuss potential future applications of phosphoproteomics in RAS research including advantages and limitations. Ultimately, phosphoproteomics represents a so far underused tool for deepening our understanding of RAS signaling and unveiling novel therapeutic targets.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding glucose metabolism and insulin action at the blood–brain barrier: Implications for brain health and neurodegenerative diseases","authors":"Yiyi Zhu,&nbsp;Alexei Verkhratsky,&nbsp;Hui Chen,&nbsp;Chenju Yi","doi":"10.1111/apha.14283","DOIUrl":"10.1111/apha.14283","url":null,"abstract":"<p>The blood–brain barrier (BBB) is a highly selective, semipermeable barrier critical for maintaining brain homeostasis. The BBB regulates the transport of essential nutrients, hormones, and signaling molecules between the bloodstream and the central nervous system (CNS), while simultaneously protecting the brain from potentially harmful substances and pathogens. This selective permeability ensures that the brain is nourished and shielded from toxins. An exception to this are brain regions, such as the hypothalamus and circumventricular organs, which are irrigated by fenestrated capillaries, allowing rapid and direct response to various blood components. We overview the metabolic functions of the BBB, with an emphasis on the impact of altered glucose metabolism and insulin signaling on BBB in the pathogenesis of neurodegenerative diseases. Notably, endothelial cells constituting the BBB exhibit distinct metabolic characteristics, primarily generating ATP through aerobic glycolysis. This occurs despite their direct exposure to the abundant oxygen in the bloodstream, which typically supports oxidative phosphorylation. The effects of insulin on astrocytes, which form the glial limitans component of the BBB, show a marked sexual dimorphism. BBB nutrient sensing in the hypothalamus, along with insulin signaling, regulates systemic metabolism. Insulin modifies BBB permeability by regulating the expression of tight junction proteins, angiogenesis, and vascular remodeling, as well as modulating blood flow in the brain. The disruptions in glucose and insulin signaling are particularly evident in neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, where BBB breakdown accelerates cognitive decline. This review highlights the critical role of normal glucose metabolism and insulin signaling in maintaining BBB functionality and investigates how disruptions in these pathways contribute to the onset and progression of neurodegenerative diseases.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}