Acta Physiologica最新文献

{"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}

{"title":"Mechanisms of Homoarginine: Looking Beyond Clinical Outcomes","authors":"Ashley Zubkowski,&nbsp;Amanda N. Sferruzzi-Perri,&nbsp;David S. Wishart","doi":"10.1111/apha.14273","DOIUrl":"10.1111/apha.14273","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>Homoarginine (hArg) is an arginine metabolite that has been known for years, but its physiological role in the body remains poorly understood. For instance, it is well known that high hArg concentrations in the blood are protective against several disease states, yet the mechanisms behind these health benefits are unclear. This review compiles what is known about hArg, namely its synthetic pathways, its role in different diseases and conditions, and its proposed mechanisms of action in humans and experimental animals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Findings</h3>\u0000 \u0000 <p>Previous work has identified multiple pathways that control hArg synthesis and degradation in the body. Furthermore, endogenous hArg can modulate the cardiovascular system, with decreased hArg being associated with cardiovascular complications and increased mortality. Studies also suggest that hArg could serve as a diagnostic biomarker for a variety of immune, pancreatic, renal, and hepatic dysfunctions. Finally, in women, hArg concentrations rapidly increase throughout pregnancy and there are suggestions that alterations in hArg could indicate pregnancy complications like pre-eclampsia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Summary</h3>\u0000 \u0000 <p>Homoarginine is an under-appreciated amino acid with potential wide-ranging roles in systemic health, pregnancy, and pathophysiology. Although recent research has focused on its health or disease associations, there is a need for more investigations into understanding the mechanistic pathways by which hArg may operate. This could be aided using metabolomics, which provides a comprehensive approach to correlating multiple metabolites and metabolic pathways with physiological effects. Increasing our knowledge of hArg's roles in the body could pave the way for its routine use as both a diagnostic and therapeutic molecule.</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/PMC11737358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996606","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":"Anatomical mapping of neural lineages expressing the transient receptor potential vanilloid type 1 receptor using a modified and combined PACT and CUBIC protocol for rapid tissue clearance","authors":"Oliver Kitzerow,&nbsp;Samuel Christensen,&nbsp;Juan Hong,&nbsp;Ryan J. Adam,&nbsp;Irving H. Zucker,&nbsp;Heather Jensen-Smith,&nbsp;Han-Jun Wang","doi":"10.1111/apha.14275","DOIUrl":"10.1111/apha.14275","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Tissue clearance is a rapidly evolving technology that allows for the three-dimensional imaging of intact biological tissues. Preexisting tissue-clearing techniques, such as Passive Clarity Technique (PACT) and Clear Unobstructed Brain Imaging Cocktails and Computational Analysis (CUBIC), clear tissues adequately but have distinct disadvantages, such as taking extensive time to clear tissues and degradation of endogenous tissue fluorescence. We developed a new tissue-clearing technique combining PACT and CUBIC protocols to map the neural lineages expressing the transient receptor potential vanilloid type 1 (TRPV1) receptor.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To test the effectiveness of this modified protocol, a TdTomato reporter mouse line was crossed with a separate mouse line containing Cre recombinase under the control of the TRPV1 promoter, which would result in TRPV1 cell lineages expressing green fluorescence protein (GFP).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared to the PACT protocol that requires several weeks to months for tissue clearance, our approach reached a satisfactory clearance within 3 days in all neural tissues as well as several non-neural tissues such as colon, duodenum, and pancreas. Compared to the CUBIC approach, all tissues reserved strong GFP fluorescence. Robust GFP fluorescence was visualized in sensory neuronal soma but not in sympathetic ganglia neuronal soma. On the other hand, GFP fluorescence in the TRPV1 cells appeared to be expressed throughout the epithelium of the duodenum and colon and the arteriole smooth muscle in all non-neuronal tissues.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study shows that our combined PACT and CUBIC (CPC) protocol can clear tissues in significantly less time while preserving tissue integrity and fluorescence.</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/PMC11737471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996602","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":"Ca2+ excitability of glia to neuromodulator octopamine in Drosophila living brain is greater than that of neurons","authors":"Urška Černe,&nbsp;Anemari Horvat,&nbsp;Ena Sanjković,&nbsp;Nika Kozoderc,&nbsp;Marko Kreft,&nbsp;Robert Zorec,&nbsp;Nicole Scholz,&nbsp;Nina Vardjan","doi":"10.1111/apha.14270","DOIUrl":"10.1111/apha.14270","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Octopamine in the <i>Drosophila</i> brain has a neuromodulatory role similar to that of noradrenaline in mammals. After release from Tdc2 neurons, octopamine/tyramine may trigger intracellular Ca²⁺ signaling via adrenoceptor-like receptors on neural cells, modulating neurotransmission. Octopamine/tyramine receptors are expressed in neurons and glia, but how each of these cell types responds to octopamine remains elusive. This study aimed to characterize Ca²⁺ responses of neurons and astrocytes to neuromodulatory octopamine signals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We expressed Ca²⁺ indicator jGCaMP7b in specific cell type in adult <i>Drosophila</i> brains and performed intracellular Ca²⁺ imaging in the brain optic lobes upon bath application of octopamine by confocal microscopy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Octopamine-stimulated Ca²⁺ responses in neurons were different from those of glial cells. The amplitude of octopamine-mediated Ca²⁺ signals in neurons was 3.4-fold greater than in astrocytes. However, astrocytes were more sensitive to octopamine; the median effective concentration that triggered Ca²⁺ responses was nearly 6-fold lower in astrocytes than in neurons. In both cell types, Ca²⁺ transients are shaped by G_q and G_s protein-coupled octopamine/tyramine receptors. Our snRNA-seq database screening uncovered differential expression patterns of these receptors between brain cell types, which may explain the difference in Ca²⁺ signaling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In the brain optic lobes, astrocytes, not neurons, appear to be the sole responders to low concentration octopamine signals, and therefore likely drive synaptic plasticity and visual processing. Given the interconnectivity of the optic lobes with other brain regions, octopaminergic signals acting through the optic lobe astrocytes may also influence higher-order brain functions including learning and memory.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968887","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":"Conference details","authors":"","doi":"10.1111/apha.14252","DOIUrl":"10.1111/apha.14252","url":null,"abstract":"<p>\u0000 <b>7^th CONGRESS OF PHYSIOLOGY AND INTEGRATIVE BIOLOGY, 91^st Congress of French Physiological Society, Tours, France, 5–7 June, 2024</b>\u0000 </p><p>\u0000 www.societedephysiologie.org\u0000 </p><p>NATIONAL ORGANIZING COMMITTEE</p><p>Ruddy RICHARD (President), Bruno Chenuel (Vice President), Dominique SIGAUDO-ROUSSEL (President of the Scientific committee), Emmanuelle Vidal Petiot (General Secretary)</p><p>RESPONSIBLE OF THE EDITION</p><p>Naim KHAN, Secretary, International Affairs</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 S732","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14252","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142976736","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":"Machine learning-based blood pressure estimation using impedance cardiography data","authors":"T. L. Bothe,&nbsp;A. Patzak,&nbsp;O. S. Opatz,&nbsp;V. Heinz,&nbsp;N. Pilz","doi":"10.1111/apha.14269","DOIUrl":"10.1111/apha.14269","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Accurate blood pressure (BP) measurement is crucial for the diagnosis, risk assessment, treatment decision-making, and monitoring of cardiovascular diseases. Unfortunately, cuff-based BP measurements suffer from inaccuracies and discomfort. This study is the first to access the feasibility of machine learning-based BP estimation using impedance cardiography (ICG) data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed ICG data from 71 young and healthy adults. Nine different machine learning algorithms were evaluated for their BP estimation performance against quality controlled, oscillometric (cuff-based), arterial BP measurements during mental (Trier social stress test), and physical exercise (bike ergometer). Models were optimized to minimize the root mean squared error and their performance was evaluated against accuracy and regression metrics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The multi-linear regression model demonstrated the highest measurement accuracy for systolic BP with a mean difference of −0.01 mmHg, a standard deviation (SD) of 10.79 mmHg, a mean absolute error (MAE) of 8.20 mmHg, and a correlation coefficient of <i>r</i> = 0.82. In contrast, the support vector regression model achieved the highest accuracy for diastolic BP with a mean difference of 0.15 mmHg, SD = 7.79 mmHg, MEA = 6.05 mmHg, and a correlation coefficient of <i>r</i> = 0.51.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The study demonstrates the feasibility of ICG-based machine learning algorithms for estimating cuff-based reference BP. However, further research into limiting biases, improving performance, and standardized validation is needed before clinical use.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968856","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":"Postnatal development of vasoactive intestinal polypeptide-expressing GABAergic interneurons in mouse somatosensory cortex","authors":"Clara A. Simacek,&nbsp;Sergei Kirischuk,&nbsp;Thomas Mittmann","doi":"10.1111/apha.14265","DOIUrl":"10.1111/apha.14265","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Despite dysfunctional vasoactive intestinal polypeptide-positive interneurons (VIP-INs) being linked to the emergence of neurodevelopmental disorders, the temporal profile of VIP-IN functional maturation and cortical network integration remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Postnatal VIP-IN development was traced with patch clamp experiments in the somatosensory cortex of <i>Vip-IRES-cre x tdTomato</i> mice. Age groups were chosen during barrel field formation, before and after activation of main sensory inputs, and in adult animals (postnatal days (P) P3–4, P8–10, P14–16, and P30–36).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Changes in passive and active membrane properties show a maturation towards accelerated signal integrations. Excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) showed progressive VIP-IN integration into cortical networks, likely via synaptogenesis: mEPSC frequency increased before P8–10, while mIPSC frequency increased at P14–16. Only mIPSC kinetics became accelerated, and the <i>E</i>/<i>I</i> ratio of synaptic inputs, defined as a ratio of mEPSC to mIPSC charge transfer, remained constant throughout the investigated developmental stages. Evoked (e)EPSCs and (e)IPSCs showed increased amplitudes, while only eIPSCs demonstrated faster kinetics. eEPSCs and eIPSCs revealed a paired-pulse facilitation by P14–16, indicating probably a decrease in the presynaptic release probability (<i>p</i>_<i>r</i>) and a paired-pulse depression in adulthood. eIPSCs also showed the latter, suggesting a decrease in <i>p</i>_<i>r</i> for both signal transmission pathways at this time point.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>VIP-INs mature towards faster signal integration and pursue different strategies to avoid overexcitation. Excitatory and inhibitory synaptic transmission become stronger and shorter via different pre- and postsynaptic alterations, likely promoting the execution of active whisking.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968858","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":"Real-time detection of somatostatin release from single islets reveals hypersecretion in type 2 diabetes","authors":"Mingyu Yang,&nbsp;Kousik Mandal,&nbsp;Moa Södergren,&nbsp;Özge Dumral,&nbsp;Lena Winroth,&nbsp;Anders Tengholm","doi":"10.1111/apha.14268","DOIUrl":"10.1111/apha.14268","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Somatostatin from pancreatic δ-cells is a paracrine regulator of insulin and glucagon secretion, but the release kinetics and whether secretion is altered in diabetes is unclear. This study aimed to improve understanding of somatostatin secretion by developing a tool for real-time detection of somatostatin release from individual pancreatic islets.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Reporter cells responding to somatostatin with cytoplasmic Ca²⁺ concentration ([Ca²⁺]_i) changes were generated by co-expressing somatostatin receptor SSTR2, the G-protein Gα15 and a fluorescent Ca²⁺ sensor in HeLa cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Somatostatin induced dose-dependent [Ca²⁺]_i increases in reporter cells with half-maximal and maximal effects at 1.6 ± 0.4 and ~30 nM, respectively. Mouse and human islets induced reporter cell [Ca²⁺]_i elevations that were inhibited by the SSTR2 antagonist CYN154806. Depolarization of islets by high K⁺, K_ATP channel blockade or increasing the glucose concentration from 3 to 11 mM evoked concomitant elevations of [Ca²⁺]_i in islets and reporter cells. Exposure of islets to glucagon, GLP-1 and ghrelin also triggered reporter cell [Ca²⁺]_i responses, whereas little effect was obtained by islet exposure to insulin, glutamate, GABA and urocortin-3. Islets from type 2 diabetic human donors induced higher reporter cell [Ca²⁺]_i responses at 11 mM and after K⁺ depolarization compared with non-diabetic islets, although fewer δ-cells were identified by immunostaining.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Type 2 diabetes is associated with hypersecretion of somatostatin, which has implications for paracrine regulation of insulin and glucagon secretion. The new reporter cell assay for real-time detection of single-islet somatostatin release holds promise for further studies of somatostatin secretion in islet physiology and pathophysiology.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968868","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 superior cervical ganglia lymph node mimicry and its role in rat ventricular arrhythmias following myocardial infarction","authors":"Qingxia Yu,&nbsp;Yan Li,&nbsp;Wenju Yan,&nbsp;Weizhong Han,&nbsp;Qian Liu,&nbsp;Junyi Zhang,&nbsp;Xiaolu Li,&nbsp;Yugen Shi,&nbsp;Yu Wang,&nbsp;Jie Yin,&nbsp;Suhua Yan","doi":"10.1111/apha.14279","DOIUrl":"10.1111/apha.14279","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Sympathetic overactivation may lead to severe ventricular arrhythmias (VAs) post-myocardial infarction (MI). The superior cervical ganglion (SCG) is an extracardiac sympathetic ganglion which regulates cardiac autonomic tone. We aimed to investigate the characteristics and functional significance of SCG on neuro-cardiac communication post-MI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Constructed MI rat model by left anterior descending coronary artery ligation, and electrophysiological, SCG sympathetic nerve activity testing, echocardiography and histology study were performed. The proteins and gene expression were detected using RNA-seq, spatial transcriptomics, quantitative PCR, and western blotting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The SCG neuronal remodeling was recognized by significant increase in adrenergic tyrosine hydroxylase (TH) (+) neurons and decrease in neuronal size. Top differentially expressed genes enriched in pro-inflammatory profile and nerve regulatory factor in left SCG (LSCG) post-MI. Interleukin (IL)-1β and IL-6 increased significantly at Day 3, ahead of nerve growth factor (NGF) which peaked at Day 7 post-MI. Spatial transcriptomics further identified the relativity of TH enrichment with macrophages and cytokines. Therapeutic LSCG-ectomy successfully triggered cardiac denervation and improved VA vulnerability. Eventually, cardiac denervation attenuated macrophage/mast cell infiltration at para-infarct regions, thus improved cardiac dysfunction. Mechanism study revealed that genetic knockdown of NGF receptor trkA in LSCG reversed sympathetic remodeling and cardiac inflammation, which may be partially mediated by substance P and calcitonin gene-related peptide (CGRP).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Extracardiac sympathetic LSCG remodeling participated in arrhythmogenesis and cardiac inflammation/function post-MI. NGF bridged neuro-immune crosstalk between pro-inflammatory shifting and sympathetic overdrive. Targeting LSCG modification facilitated cardiac protection and prevented VAs post-MI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 2","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968854","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}