Acta Physiologica最新文献

{"title":"Targeting Inflammation in Type 2 Diabetes: The Emerging Role of Decorin","authors":"Shayla Sharmine, Luiza Ghila","doi":"10.1111/apha.70049","DOIUrl":"https://doi.org/10.1111/apha.70049","url":null,"abstract":"<p>Type 2 diabetes (T2D) is a metabolic disease characterized by insulin resistance and progressive deterioration of pancreatic insulin-producing β-cell function, leading to chronic hyperglycemia. Although initially considered a “disease of the pancreas,” latest views acknowledge that optimal glycemic regulation involves complex and mutual communication between different organs and tissues including the pancreas, liver, intestine, brain, muscle and adipose tissue. Skeletal muscle has long been recognized as a metabolic organ [<span>1</span>], producing myokines such as irisin and interleukin-6 (IL6) with key role in modulating insulin sensitivity and metabolic health [<span>2</span>]. In a recent issue of Acta Physiologica, Langlois et al. [<span>3</span>] provides novel insight to the role of another myokine, decorin, a promising protective factor involved in preserving the pancreatic β-cell function and insulin secretion under inflammatory conditions.</p><p>Myokines are proteins that are produced and released from skeletal muscle cells and act as hormones on other organs, including the pancreas, liver, brain, and adipose tissue [<span>1</span>]. Decorin, a small leucine-rich proteoglycan [<span>4</span>], has been established as a myokine [<span>5</span>] (Figure 1), promoting muscle hypertrophy through inhibition of myostatin (MSTN, or growth and differentiation factor 8). MSTN is a member of the transforming growth factor-β (TGF-β) superfamily, having a crucial role in the negative regulation of muscle growth by suppressing both myoblast proliferation and myofibre hypertrophy. Higher levels of MSTN were detected in T2D but also in non-obese insulin-resistant patients. Also, MSTN was shown to inhibit glucose transporter 4 (GLUT4) and thus decrease muscle glucose uptake. Decorin, which binds and contributes to the stabilization of collagen fibers in the extracellular matrix (ECM) was shown to be produced by muscle activity and to sequester MSTN in the ECM, thus blocking its inhibitory effect on myoblast proliferation [<span>6</span>] and potentially having also an indirect role in glucose regulation. But, can decorin act long-range as well?</p><p>Langlois et al. provided significant experimental insights into this muscle-pancreatic islet crosstalk by showing that decorin could also have a direct role on pancreatic islet cells. Applied in vitro, decorin protected the isolated β-cells and pancreatic islets from inflammatory stress. Recent studies showed that chronic low-grade inflammation leads to insulin signaling disruption, thus exacerbating β-cell stress leading to functional dysfunction and eventual cell loss [<span>7, 8</span>]. Moreover, elevated levels of pro-inflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and interferon γ (IFN-γ) were previously shown to hinder glucose homeostasis and increase metabolic stress. Exposure to TNF-α typically impairs glucose-stimulated insulin secretion (GSIS), disrupt","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 6","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143875513","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":"Hemodynamics and Drinking in the Giraffe","authors":"Christian Aalkjær,&nbsp;Mads Damkjær,&nbsp;Ulrik T. Baandrup,&nbsp;Mads F. Bertelsen,&nbsp;Torbjørn Brøgger,&nbsp;Emil Brøndum,&nbsp;Carl C. Danielsen,&nbsp;Jonas A. Funder,&nbsp;Carsten Grøndahl,&nbsp;J. Michael Hasenkam,&nbsp;Per G. Henriksen,&nbsp;Niels H. Secher,&nbsp;Nini Skovgaard,&nbsp;Morten H. Smerup,&nbsp;Niklas Telinius,&nbsp;Kristine H. Østergaard,&nbsp;Peter Bie,&nbsp;Tobias Wang","doi":"10.1111/apha.70046","DOIUrl":"https://doi.org/10.1111/apha.70046","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The circulation of 4–6 m tall giraffes is markedly affected by gravity. To ensure cerebral perfusion, upright giraffes generate a blood pressure in excess of 200 mmHg. Before drinking, the head is lowered by 3–5 m, providing exceptional hemodynamic challenges. Here, we provide quantitative hemodynamic measures during head movement and drinking.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We measured carotid pressure, jugular pressure, heart rate, and blood flow in awake giraffes, along with circulating blood volume and cerebrospinal fluid pressure in anesthetized giraffes. We also analyzed the contractility and innervation of isolated cerebral and extracranial arteries, and the mechanical properties of jugular veins.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>When heads were lowered for drinking (i) blood pressure at heart level decreased but increased again during drinking, (ii) jugular pressure increased and oscillated during drinking, (iii) heart rate fell, (iv) carotid blood flow was unchanged, while cephalic hemodynamic resistance increased, and (vi) cranial cerebrospinal fluid pressure increased. Small cerebral arteries exhibited strong myogenic responses, particularly at around 100 mmHg, while extracranial arteries responded at higher pressures (200–250 mmHg). The giraffe's blood volume was small and blood pressure sensitive to minor reductions in blood volume.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Central blood pressure decreased when the head was lowered, but drinking per se caused a surprising rise in blood pressure to pre-drinking levels. This rise in blood pressure is likely due to the transfer of esophageal water boli acting on the jugular veins. The cephalic capillaries are protected by a strong myogenic response and sympathetic innervation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143856894","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":"Calcineurin Inhibitor Associated Nephrotoxicity in Kidney Transplantation—A Transplant Nephrologist's Perspective","authors":"Carla M. Hansen,&nbsp;Sebastian Bachmann,&nbsp;Mingzhen Su,&nbsp;Klemens Budde,&nbsp;Mira Choi","doi":"10.1111/apha.70047","DOIUrl":"https://doi.org/10.1111/apha.70047","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Calcineurin inhibitors (CNIs) have revolutionized transplant medicine, improving allograft survival but posing challenges like calcineurin inhibitor-induced nephrotoxicity (CNT). Acute CNT, often dose-dependent, leads to vasoconstriction and acute kidney injury, with treatment focusing on CNI exposure reduction. Chronic CNT manifests as progressive allograft function decline, with challenges in distinguishing it from nonspecific allograft nephropathy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This narrative review provides a concise overview of the clinical management of CNT, covering acute and chronic CNT. We reviewed original articles, landmark papers, and meta-analyses on CNT mitigation strategies, including CNI-sparing approaches.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Preventive measures include co-medications, CNI exposure monitoring, and CNI sparing strategies, such as reducing target trough levels and converting to mTOR inhibitors (mTORi) or belatacept. Despite improvements in graft function, challenges persist in demonstrating significant differences in allograft survival with CNI-sparing regimens. The paradigm shift from chronic CNT as the main cause of chronic allograft nephropathy toward rather immunologic triggered injuries and/or comorbidities as relevant contributors to allograft deterioration over time must be kept in mind.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>CNIs have significantly improved kidney transplant outcomes, but their associated nephrotoxicity necessitates mitigation strategies. The decision to implement such regimens is always an individual choice balancing against the risk of immunologic injuries. Further long-term studies are needed to optimize immunosuppressive approaches and refine CNT management.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840814","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":"Vitamin K preserves gamma-glutamyl carboxylase activity against carbamylations in uremia: Implications for vascular calcification and adjunct therapies","authors":"Nadine Kaesler,&nbsp;Suresh Kaushik,&nbsp;Janina Frisch,&nbsp;Susanne Ziegler,&nbsp;Jochen Grommes,&nbsp;Alexander Gombert,&nbsp;Leticia Prates Roma,&nbsp;Christoph Kuppe,&nbsp;Joachim Jankowski,&nbsp;Jürgen Floege,&nbsp;Sofia de la Puente-Secades,&nbsp;Rafael Kramann,&nbsp;Vera Jankowski","doi":"10.1111/apha.70040","DOIUrl":"https://doi.org/10.1111/apha.70040","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Vascular calcification contributes to morbidity and mortality in aging and is accelerated in diabetes and in chronic kidney disease. Matrix Gla Protein is a potent inhibitor of vascular calcification, which is activated by the vitamin K-dependent gamma-glutamyl carboxylase (GGCX). However, through a currently unidentified mechanism, the activity of GGCX is reduced in experimental uremia, thereby contributing to the promotion of vascular calcifications. In this study, we aim to identify the cause of these functional alterations and to stimulate the enzyme activity by potential GGCX binding compounds as a new avenue of therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Two rodent models of experimental uremia and human carotid plaques were assessed for GGCX activity and modifications, as well as calcification. In silico compound screening via BindScope identified potential binding partners of GGCX which were further validated in functional assays for enzymatic activity changes and for in vitro calcification. Mass spectrometry was applied to monitor molecular mass changes of the GGCX.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Mass spectrometry analysis revealed post-translational modifications of the GGCX in uremic rats and mice, as well as in calcified human carotid plaques. Functional assays showed that the post-translational carbamylation of GGCX reduced the enzyme activity, which was prevented by vitamin K2. Chrysin, identified by compound screening, stimulated GGCX activity, reduced calcium deposition in VSMCs, and oxidized GGCX at lysine 517.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In conclusion, this study clearly demonstrates that the vitamin K-dependent enzyme GGCX plays a significant role in uremic calcification and may be modulated to help prevent pathological changes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801334","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":"Cav3.1 T-Type Calcium Channel Acts as a Gateway for GABAergic Excitation in the Medial Prefrontal Cortex That Leads to Chronic Psychological Stress Responses in Mice","authors":"Yasushi Yabuki,&nbsp;Karin Hori,&nbsp;Zizhen Zhang,&nbsp;Kazuya Matsuo,&nbsp;Kenta Kudo,&nbsp;Shingo Usuki,&nbsp;Vinicius M. Gadotti,&nbsp;Lina Chen,&nbsp;Shinya Ueno,&nbsp;Shuji Chiba,&nbsp;Kohji Fukunaga,&nbsp;Gerald W. Zamponi,&nbsp;Norifumi Shioda","doi":"10.1111/apha.70043","DOIUrl":"https://doi.org/10.1111/apha.70043","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The molecular mechanisms of chronic stress-induced psychiatric disorders, including depression, remain unknown. The current study aimed to assess the role of Cav3.1 T-type calcium channels as a gateway for the chronic stress-induced activation of parvalbumin (PV)-positive gamma-aminobutyric acidergic (GABAergic) neurons in the medial prefrontal cortex (mPFC) of mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The function of the Cav3.1 T-type calcium channel in the mouse mPFC following chronic stress was investigated using behavioral tests, electrophysiological analyses, transcriptome analyses, and optogenetic approaches.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Cav3.1-knockout (Cav3.1^−/−) mice were resistant to chronic stress-induced depressive-like behaviors induced by repeated forced-swimming test or tail-suspension test. Immunohistochemical analysis revealed that Cav3.1 was predominantly localized in PV-positive GABAergic neurons in the mPFC. Based on transcriptomic and electrophysiological analyses, the excitatory–inhibitory (E–I) balance was disrupted by the chronic stress-induced activation of PV-positive GABAergic neurons in the mPFC of wild-type (WT) mice, but not in that of Cav3.1^−/− mice. Optogenetic control of PV-positive GABAergic neurons in the mPFC revealed that they played a pivotal role in depressive-like behaviors. The administration of TTA-A2, a selective T-type calcium channel antagonist, reduced chronic stress-induced depressive-like behaviors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The Cav3.1 T-type calcium channel acts as a gateway for the activation of GABAergic neurons in the mPFC of mice, thereby eliciting chronic psychobiological stress responses.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143793466","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":"New Editor-in-Chief for Acta Physiologica","authors":"Tobias Wang","doi":"10.1111/apha.70044","DOIUrl":"https://doi.org/10.1111/apha.70044","url":null,"abstract":"&lt;p&gt;I assumed the role of Editor-in-Chief of &lt;i&gt;Acta Physiologica&lt;/i&gt; with equal measures of awe and pride at the very start of 2025. Awe because I must fill the shoes of my predecessor Professor Pontus Persson [&lt;span&gt;1&lt;/span&gt;], who competently led the journal for more than a decade with great dedication and ability. The pride is obviously instilled from becoming part of an almost 140-year physiology legacy at the highest level possible. &lt;i&gt;Acta Physiologica&lt;/i&gt; is indeed ranked amongst the world's best general physiology journals and enjoys widespread respect amongst authors and readers in all physiological disciplines.&lt;/p&gt;&lt;p&gt;In addition to awe and pride, I confess that the role as EiC for &lt;i&gt;Acta Physiologica&lt;/i&gt; also instills a component of anxiety. Academic publishing is currently entering troubled waters where the old supertankers, that is, the society journals, are in danger of being derailed by predatory journals that weigh financial interest higher than the pursuit of knowledge and the classic academic virtues. The society journals, however, have much to offer, and &lt;i&gt;Acta Physiologica&lt;/i&gt;, for example, channels revenues into academic activities with support to meetings, conferences, and travel grants. &lt;i&gt;Acta Physiologica&lt;/i&gt; therefore contributes to building the physiological community at all stages in an academic career.&lt;/p&gt;&lt;p&gt;As an additional merit, &lt;i&gt;Acta Physiologica&lt;/i&gt; has been the official &lt;i&gt;Journal of the Federation of European Physiological Societies&lt;/i&gt; (FEPS) for more than three decades, and we are currently expanding our editorial board to be more international in line with the ongoing and welcome internationalization of physiological sciences.&lt;/p&gt;&lt;p&gt;I firmly believe that general physiology journals, such as &lt;i&gt;Acta Physiologica&lt;/i&gt;, that cover many processes within all bodily organs and tissues are important because they emphasize the integration of processes that span from molecular structures to the whole organism. In addition to the “vertical” integration at various levels of biological organization, physiology also arises from the “horizontal” interplay between organ systems. Both vertical and horizontal interactions are of paramount importance for animals and humans to maintain homeostasis during normal behaviors and physiological states, including sleep [&lt;span&gt;2&lt;/span&gt;], exercise [&lt;span&gt;3&lt;/span&gt;], digestion [&lt;span&gt;4&lt;/span&gt;], and pregancy [&lt;span&gt;5&lt;/span&gt;] and to understand how we respond to environmental perturbances, such as hypoxia [&lt;span&gt;6&lt;/span&gt;], hypercapnia [&lt;span&gt;7&lt;/span&gt;], or extreme temperatures [&lt;span&gt;8&lt;/span&gt;]. In combination with diurnal and annual cycles [&lt;span&gt;9, 10&lt;/span&gt;], the homeostatic regulation by virtue of endocrine and neural mechanisms of humans and animals is therefore as exciting as ever!&lt;/p&gt;&lt;p&gt;In my own research, I am highly motivated to understand organismal function, and I characterize myself as an integrative physiologist that seeks to understand the unifying principles in physiology. Wit","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70044","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770035","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":"Pharmaceutical prokinetic and surgical interventions have opposing effects on gastroduodenal electromechanical coupling","authors":"Sam Simmonds,&nbsp;Tim H.-H. Wang,&nbsp;Ashton Matthee,&nbsp;Jarrah M. Dowrick,&nbsp;Andrew J. Taberner,&nbsp;Peng Du,&nbsp;Timothy R. Angeli-Gordon","doi":"10.1111/apha.70024","DOIUrl":"https://doi.org/10.1111/apha.70024","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Improper gastric emptying is implicated in several gastrointestinal disorders and may result from disrupted electromechanical coupling of the gastroduodenal junction (GDJ). Rhythmic “slow waves” and myogenic “spikes” are bioelectrical mechanisms that, alongside neural and hormonal co-factors, control GDJ motility.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To characterize the electromechanical effects of prokinetic (erythromycin) infusion and truncal vagotomy on pre-clinical in vivo porcine models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Following ethical approval, the GDJ was exposed in anesthetized crossbreed weaner pigs (<i>N</i> = 10), and custom high-resolution electrodes were applied to the serosal surface. An EndoFLIP catheter (Medtronic, USA) was inserted orally and positioned across the pylorus to measure luminal diameter. In all subjects, control periods preceded intravenous infusion of erythromycin. In five of those subjects, truncal vagotomy was performed approximately an hour post-infusion, before recording was resumed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared to control recordings, erythromycin increased contractile amplitude ([2.9 ± 1.1] mm vs. [2.2 ± 0.9] mm; <i>p</i> = 0.002) and was associated with more consistent gastric slow-wave rhythms and increased amplitude of slow waves and spikes. Surgical vagotomy immediately decreased contractile amplitude ([2.90 ± 1.1] mm vs. [1.2 ± 0.6] mm; <i>p</i> = 0.049) and was associated with reduced slow-wave amplitude, increased gastric and duodenal slow-wave frequencies, and decreased spike patch coverage.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In conclusion, prokinetics and vagotomy produced opposing effects on GDJ electromechanical coupling and could inform diagnostic and interventional practices for patients with pathophysiological complications of this region.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778176","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":"Glucose absorption by isolated, vascularly perfused rat intestine: A significant paracellular contribution augmented by SGLT1 inhibition","authors":"Cecilie Bæch-Laursen,&nbsp;Rune Kuhre Ehrenreich,&nbsp;Ida Marie Modvig,&nbsp;Simon Veedfald,&nbsp;Jens Juul Holst","doi":"10.1111/apha.70033","DOIUrl":"https://doi.org/10.1111/apha.70033","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Intestinal glucose transport involves SGLT1 in the apical membrane of enterocytes and GLUT2 in the basolateral membrane. In vivo studies have shown that absorption rates appear to exceed the theoretical capacity of these transporters, suggesting that glucose transport may occur via additional pathways, which could include passive mechanisms. The aim of the study was to investigate glucose absorption in an in vitro model, which has proven useful for endocrine studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We studied both transcellular and paracellular glucose absorption in the isolated vascularly perfused rat small intestine. Glucose absorbed from the lumen was traced with ¹⁴C-<span>d</span>-glucose, allowing sensitive and accurate quantification. SGLT1 and GLUT2 activities were blocked with phlorizin and phloretin. ¹⁴C-<span>d</span>-mannitol was used as an indicator of paracellular absorption.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our results indicate that glucose absorption in this model involves two transport mechanisms: transport mediated by SGLT1/GLUT2 and a paracellular transport mechanism. Glucose absorption was reduced by 60% when SGLT1 transport was blocked and by 80% when GLUT2 was blocked. After combined luminal SGLT1 and GLUT2 blockade, ~30% of glucose absorption remained. <span>d</span>-mannitol absorption was greater in the proximal small intestine compared to the distal small intestine. Unexpectedly, mannitol absorption increased markedly when SGLT1 transport was blocked.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In this model, glucose absorption occurs via both active transcellular and passive paracellular transport, particularly in the proximal intestine, which is important for the understanding of, for example, hormone secretion related to glucose absorption. Interference with SGLT1 activity may lead to enhanced paracellular transport, pointing to a role in the regulation of the latter.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778174","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":"Deficiency of the Synaptic Adhesion Protein Leucine-Rich Repeat Transmembrane Protein 4 Like 1 Affects Anxiety and Aggression in Zebrafish","authors":"Eva Tatzl,&nbsp;Giulia Petracco,&nbsp;Isabella Faimann,&nbsp;Marco Balasso,&nbsp;Agnes Anna Mooslechner,&nbsp;Thomas Bärnthaler,&nbsp;Giovanny Rodriguez-Blanco,&nbsp;Florian Reichmann","doi":"10.1111/apha.70042","DOIUrl":"https://doi.org/10.1111/apha.70042","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Leucine-rich repeat transmembrane proteins (LRRTMs) are synaptic adhesion proteins that regulate synapse development and function. They interact transsynaptically with presynaptic binding partners to promote presynaptic differentiation. Polymorphisms of <i>LRRTM4</i>, one of the four members of this protein family, have been linked to multiple neuropsychiatric disorders and childhood aggression, but the underlying mechanisms and physiological function of LRRTM4 during behavior are currently unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To characterize the role of this gene for brain function, we combined a battery of behavioral assays with transcriptomic and metabolomic analyses, using zebrafish as a model system.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our findings revealed that <i>lrrtm4l1</i>, a brain-specific zebrafish orthologue of human <i>LRRTM4</i>, exhibits a brain region-specific expression pattern similar to humans, with strong expression in the dorsal telencephalon, a brain area critical for regulating emotional-affective and social behavior. <i>lrrtm4l1</i>^−/− zebrafish displayed heightened anxiety and reduced aggression, while locomotion and social behavior remained unaffected by the gene knockout. Transcriptomic analysis of the telencephalon identified over 100 differentially expressed genes between wild-type and mutant zebrafish and an enrichment of pathways related to synaptic plasticity and neuronal signaling. The brain metabolome of <i>lrrtm4l1</i>^−/− zebrafish showed multiple alterations, particularly in the dopaminergic and adenosinergic neurotransmitter systems.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings suggest that LRRTMs may have functions beyond their established role in excitatory synapse development, such as the regulation of neurotransmission and behavior. Targeting LRRTM4 therapeutically may thus be an interesting novel approach to alleviate excessive aggression or anxiety associated with a number of neuropsychiatric conditions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770034","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 Pancreatic Islets Reveals δ-Cell Dysfunction in Type 2 Diabetes","authors":"Mototsugu Nagao","doi":"10.1111/apha.70045","DOIUrl":"https://doi.org/10.1111/apha.70045","url":null,"abstract":"&lt;p&gt;Pancreatic δ-cells are endocrine cells located within the islets of Langerhans and are primarily responsible for secreting somatostatin. Although δ-cells represent a minority population within the islets—approximately 5% of the total islet cells—they play an important role in modulating glucagon and insulin secretion through paracrine regulatory effects of somatostatin on neighboring α- and β-cells. Classically, somatostatin has been well recognized as a potent inhibitor of glucagon and insulin secretion. Recent research, however, has underscored that δ-cells mediate these inhibitory effects not only through diffusible paracrine signaling but also via direct cell-to-cell contacts, facilitated by δ-cell processes extending toward neighboring α- and β-cells [&lt;span&gt;1&lt;/span&gt;]. Moreover, advanced imaging techniques and patch-clamp electrophysiological recordings have revealed synchronized calcium oscillations between δ- and β-cells, [&lt;span&gt;2, 3&lt;/span&gt;] highlighting tightly coordinated secretory dynamics within the islet microenvironment. A recent study in &lt;i&gt;Acta Physiologica&lt;/i&gt; by Yang et al. [&lt;span&gt;4&lt;/span&gt;] significantly advances our understanding by introducing a novel method for the real-time visualization of somatostatin secretion, revealing δ-cell dysfunction in type 2 diabetes.&lt;/p&gt;&lt;p&gt;Abnormalities in these δ-cell-mediated interactions have been reported in pathological conditions such as diabetes. Dysfunctional communication among δ-, α-, and β-cells, [&lt;span&gt;2, 5&lt;/span&gt;] along with impaired or dysregulated somatostatin secretion, [&lt;span&gt;1&lt;/span&gt;] disrupts hormonal balance and compromises glucose homeostasis. Accurate visualization of these δ-cell-mediated intercellular interactions, including real-time imaging of somatostatin secretion dynamics at the single islet level, is therefore critical not only for elucidating the overall mechanisms governing hormone secretion within islets but also for advancing our understanding of diabetes pathophysiology and identifying novel therapeutic targets. However, traditional immunoassays used to measure somatostatin have limited sensitivity and temporal resolution, which obscures accurate evaluation of somatostatin secretion dynamics at the single islet level.&lt;/p&gt;&lt;p&gt;To overcome the limitations associated with conventional immunoassays, Yang et al. developed an innovative real-time reporter cell assay to analyze somatostatin secretion dynamics at the single islet level. Specifically, the authors engineered HeLa cells to serve as highly sensitive reporter cells expressing somatostatin receptor subtype 2 (SSTR2), which is functionally coupled via the G-protein subunit Gα15 to phospholipase C-dependent intracellular calcium signaling pathways (Figure 1). Upon binding of somatostatin to SSTR2, the receptor cells exhibit a measurable intracellular calcium oscillation via fluorescence emitted by the genetically encoded calcium indicator R-GECO1, enabling precise real-time detection and quantification of somato","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"241 5","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70045","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770033","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}