Acta Physiologica最新文献

{"title":"The Reservoir Gate Theory: Microcirculatory Changes Involving Neurovascular Units After Traumatic Brain Injury","authors":"Dan Ye,&nbsp;Long Lin,&nbsp;Shuling Chen,&nbsp;Shousen Wang","doi":"10.1111/apha.70315","DOIUrl":"10.1111/apha.70315","url":null,"abstract":"<div>\u0000 \u0000 <p>Traumatic brain injury is one of the leading causes of death and disability worldwide, and its pathological and physiological mechanisms are complex. In recent years, the research perspective centered on neurovascular units has revealed the crucial role of microcirculation disorders after traumatic brain injury. This article reviews the pathological manifestations of microcirculation disorders after traumatic brain injury and their interaction mechanisms with damage to various components of neurovascular units (endothelial cells, pericytes, astrocytes), and a new hypothesis of “The Reservoir Gate Theory” in brain tissue microcirculation is proposed.</p>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 11","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149072943","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":"cGMP Signaling in Arterioles Revealed by FRET-Based Real-Time Measurement in Mice In Vivo","authors":"Lukas Thiele,&nbsp;Kjestine Schmidt,&nbsp;Martin Thunemann,&nbsp;Andreas Friebe,&nbsp;Susanne Feil,&nbsp;Robert Feil,&nbsp;Cor de Wit","doi":"10.1111/apha.70317","DOIUrl":"10.1111/apha.70317","url":null,"abstract":"<p>cGMP evokes arteriolar vasorelaxation and is generated in smooth muscle by the soluble guanylyl cyclase (sGC) stimulated by endothelial NO. Phosphodiesterases (PDEs) degrade cGMP and may contribute in diameter regulation. We examined arteriolar cGMP levels in real-time in vivo upon NO and acetylcholine (ACh) and effects of PDE inhibition. Changes in cGMP were measured by FRET using the indicator protein cGi500. Arterioles in the cremaster muscle of anesthetized mice expressing cGi500 were exposed for imaging. They were stimulated with various NO donors (DEA/NO, SNP, SNAP) and ACh with or without PDE inhibition (non-specific: IBMX; PDE-5 specific: sildenafil). Furthermore, dilations induced by ACh and SNP were studied in sGC-deficient mice. DEA/NO and SNAP led to a fast, concentration-dependent rise of fluorescence ratio of cGi500 (by 4.0% at 10 μmol/L), that declined on removal slowly. These ratio changes indicated cGMP increases as verified by inhibition of the sGC using ODQ. PDE inhibition increased cGMP levels slowly despite NO synthase inhibition. However, it did not amplify NO-induced ratio increases, but the decline after drug removal was decelerated. Interestingly, ACh did not modify cGMP levels and dilations were not impaired in sGC-deficient mice. FRET-based imaging allows reliable real-time assessment of arteriolar cGMP levels in vivo. PDE activity does not limit the amplitude, but the duration of cGMP signaling after stimulation. Furthermore, we conclude that ACh does not release endothelial NO in murine arterioles. Preliminary experiments demonstrate that simultaneous measurement of cGMP and diameter is feasible using mice with expression of cGi500 in smooth muscle cells.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 11","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13616743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149068711","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":"Renin-Angiotensin Signaling and Vascular Function: Insights into Health and Disease","authors":"Giovanni Bertoldi,&nbsp;Swapnil K. Sonkusare","doi":"10.1111/apha.70321","DOIUrl":"10.1111/apha.70321","url":null,"abstract":"<p>The renin-angiotensin system (RAS) is an essential regulator of vascular structure and function, and dysregulation of angiotensin II (Ang II) signaling plays a critical role in the development of hypertension and associated vascular complications. Ang II exerts its vascular actions primarily through the angiotensin II type 1 receptor (AT1R), activating canonical and non-canonical signaling pathways that extend beyond classical G-protein-dependent signaling mechanisms. Here, we review the literature on tissue-specific RAS, Ang II-dependent and Ang II-independent signaling mechanisms of vascular Ang II receptors, and their contribution to vasoconstriction, endothelial dysfunction, vascular remodeling, and arterial stiffness in hypertension. We highlight the roles of mechanosensitive AT1R signaling, dysregulation of vascular ion channels, enhanced reactive oxygen species production, immune and inflammatory signaling, and mineralocorticoid receptor activation as key drivers of hypertensive vascular pathology. In addition, we discuss tissue-specific expression of RAS components and separation between RAS pathways underlying blood pressure elevation and vascular remodeling in hypertension. Collectively, emerging research on vascular Ang II receptor signaling reveals novel regulatory mechanisms and therapeutic opportunities beyond conventional RAS inhibition. Targeting downstream pathways that mediate oxidative stress, mechanotransduction, ion channel activity, and profibrotic signaling may offer improved strategies to prevent or reverse Ang II receptor-dependent vascular dysfunction in hypertension.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 11","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13616746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149068700","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":"Rethinking Assessment of the Human Muscle Metaboreflex: Why the Stimulus Matters","authors":"Rasmus Kopp Hansen","doi":"10.1111/apha.70320","DOIUrl":"10.1111/apha.70320","url":null,"abstract":"&lt;p&gt;In a publication titled “Innovative dose-response assessment of the metaboreflex with indirect control of intramuscular metabolic perturbation in humans” [&lt;span&gt;1&lt;/span&gt;], Kouzkouz and colleagues performed elegant experiments that shed light on the methodological assessment of the muscle metaboreflex in humans. They also report intriguing findings regarding sex differences in mean arterial pressure (MAP) responses to metaboreflex activation that challenge existing views.&lt;/p&gt;&lt;p&gt;Alongside feedforward signals from the cerebral cortex (central command), and feedback signals from the arterial and cardiopulmonary baroreflexes and the arterial chemoreflex, feedback from Group III/IV muscle afferents within the exercising muscle (i.e., the exercise pressor reflex) is instrumental for orchestrating the cardiovascular responses to exercise [&lt;span&gt;2&lt;/span&gt;]. In humans, the metabolically sensitive component of the exercise pressor reflex (i.e., the muscle metaboreflex) has been studied for almost a century. Already in 1937, Alam and Smirk [&lt;span&gt;3&lt;/span&gt;] demonstrated the concept of a chemical/metabolic reflex emerging from skeletal muscle by demonstrating that blood pressure remained elevated above resting levels when contraction-induced metabolites were trapped in the leg by circulatory occlusion of the thigh immediately upon the cessation of dynamic calf exercise in humans. Today, it is well-established, that once activated by the accumulation of metabolites produced by contracting skeletal muscle, the metaboreflex evoke an increase in sympathetic nerve activity (SNA) that, via constriction of the systemic vasculature and modulation of the chronotropic and inotropic functions of the heart, increases arterial blood pressure and supports the redistribution of blood flow during exercise [&lt;span&gt;4&lt;/span&gt;]. In addition to the exercising limb muscle metaboreflex, the stimulation of phrenic afferent fibers in response to elevated work of breathing, such as during sustained, high-intensity whole-body exercise, also evokes reflex sympathoexcitation (i.e., the respiratory metaboreflex) with consequences for blood flow distribution to the active limb muscle [&lt;span&gt;5&lt;/span&gt;] and potentially, the brain [&lt;span&gt;6&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Post-exercise circulatory occlusion (PECO) is a useful model to activate and isolate the muscle metaboreflex, as it permits investigation of metaboreceptor stimulation independent of influences from mechanoreceptor stimulation and central command. Using such experimental model, Kouzkouz and colleagues performed a dose–response assessment of the muscle metaboreflex in 30 healthy adults (15 females) using four consecutive bouts of sustained submaximal isometric knee-extension exercise of progressively longer duration, followed by 2 min of PECO [&lt;span&gt;1&lt;/span&gt;] (Figure 1). The dose–response approach allowed the authors to assess linearity of the responses to graded levels of metaboreflex activation. Metaboreflex activation (i.e., intramuscular met","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 11","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70320","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149068635","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":"Correction to “AS160 Overexpression Protects Against β-Cell Failure in Hyperglycemic Mice by Interacting With HSPA8 to Regulate Mitophagy”","authors":"","doi":"10.1111/apha.70324","DOIUrl":"10.1111/apha.70324","url":null,"abstract":"<p>\u0000 <span>W. Chen</span>, <span>Y. Lu</span>, <span>X. Liu</span>, et al., “ <span>AS160 Overexpression Protects Against β-Cell Failure in Hyperglycemic Mice by Interacting With HSPA8 to Regulate Mitophagy</span>,” <i>Acta Physiologica</i> <span>242</span>, no. <span>10</span> (<span>2026</span>): e70304. https://doi.org/10.1111/apha.70304.\u0000 </p><p>In the originally published version of this article, affiliations 1, 2, and 3 were presented as separate affiliations. These affiliations should have been combined into a single affiliation. As a result, the affiliation numbering and author affiliation assignments have been updated accordingly.</p><p>The corrected affiliation list is shown below:</p><p>Wenli Chen^1,2, Yanting Lu^3,4, Xiangxiang Liu^1,2, Bangrui Huang^1,2, Daowei Liu^1,2, Bilian He¹, Zhiming Zhao¹, Qian Wang¹, Jixi Li⁵, Wenyong Xiong¹</p><p>¹Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education; Yunnan Provincial Center for Research &amp; Development of Natural Products; School of Pharmacy, Yunnan University, Kunming, P. R. China.</p><p>²School of Life Science, Yunnan University, Kunming, P. R. China.</p><p>³State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, P. R. China.</p><p>⁴School of Medicine, Shandong University of Traditional Chinese Medicine, Jinan, P. R. China.</p><p>⁵School of Life Sciences, State Key Laboratory of Genetics and Development of Complex Phenotypes, Shanghai Engineering Research Center of Industrial Microorganisms, Fudan University, Shanghai, P. R. China.</p><p>We apologize for this error.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 11","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70324","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149068658","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":"Mouse Models of Human Renal Physiology: Informative but Imperfect","authors":"Eleanor Lederer","doi":"10.1111/apha.70322","DOIUrl":"https://doi.org/10.1111/apha.70322","url":null,"abstract":"&lt;p&gt;The recent manuscript in Acta Physiologica titled “Renal phosphate reabsorption in humans depends on at least three distinct transporters, unlike in mice” confirms what we all suspected: mouse renal physiology is not human renal physiology [&lt;span&gt;1&lt;/span&gt;]. The extensive body of work examining phosphate transport in renal proximal tubules yielded a wealth of knowledge including identification of multiple sodium coupled phosphate transporters, characterization of their properties and structures as well as their dietary and hormonal regulation [&lt;span&gt;2&lt;/span&gt;]. The studies were performed in cell culture and animal models, primarily in mice, but also in rats and a few other species. Cloning of the transporters identified crucial sites for regulation of the individual transporters, and their specific contributions were quantified through deletion experiments. Three transporters were identified and characterized in mouse kidneys: Npt2a, Npt2c, and PiT2 [&lt;span&gt;3&lt;/span&gt;]. Deletion of Npt2a produced phosphate wasting, skeletal abnormalities, and renal cortical calcifications in mice [&lt;span&gt;4&lt;/span&gt;]. Deletion of Npt2c showed essentially no mineral metabolism phenotype, suggesting a minor role possibly during growth [&lt;span&gt;5&lt;/span&gt;]. The broad expression of the third transporter, PiT2, suggested a role as a housekeeping protein to provide the proximal tubule cell with needed phosphate, its contribution to phosphate reabsorption low.&lt;/p&gt;&lt;p&gt;Although the human sodium phosphate cotransporters demonstrated substantial homology to the mouse transporters, the allocation of the roles of the sodium coupled phosphate transporters in people based on mouse studies was upended by major findings uncovered by genetics of human disease. Mutations in Npt2a in people caused Fanconi syndrome with progressive chronic kidney disease [&lt;span&gt;6&lt;/span&gt;] or Idiopathic Infantile Hypercalcemia [&lt;span&gt;6&lt;/span&gt;]. Mutations in Npt2c produced the clinical syndrome of Hereditary Hypophosphatemic Rickets with Hypercalciuria [&lt;span&gt;7&lt;/span&gt;]. Mutations in PiT2 showed no renal phenotype [&lt;span&gt;8&lt;/span&gt;]. Clearly, the relative contributions of the renal sodium phosphate cotransporters in human beings differed from those in mouse, particularly in the case of Npt2c.&lt;/p&gt;&lt;p&gt;The study by Fernandes and colleagues [&lt;span&gt;1&lt;/span&gt;] marks a significant advance in linking these clinical observations with human physiology. The authors obtained human kidney samples to correlate phosphate transport studies with phosphate transporter expression. Using kidneys from adults and neonates that had been turned down for kidney transplantation, the investigators prepared brush border membrane vesicles and performed radiolabeled phosphate uptake studies. They estimated the relative contributions of each transporter by uptake studies in the presence of a specific inhibitor of Npt2a and a general inhibitor of both SLC34 proteins. These studies were complemented by immunoblot of kidney homogenates with antibodies ","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 11","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70322","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029164","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":"Targeted Metabolomics Reveals a Metabolic Signature Derived From the Stimulation of Cells With the Specific AT2R Agonist C21","authors":"Jorge Andrés Narváez Pardo,&nbsp;Sofía Bajicoff,&nbsp;Leonie Gerling,&nbsp;Ernest Oppong-Danquah,&nbsp;Zahraa Jaber,&nbsp;Anke Schumann,&nbsp;Luciana Hannibal,&nbsp;Fernando Pablo Dominici","doi":"10.1111/apha.70314","DOIUrl":"https://doi.org/10.1111/apha.70314","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Despite increasing evidence for the cardiometabolic protective effects of angiotensin II Type 2 receptor (AT₂R) activation, the underlying molecular mechanisms remain incompletely understood. This study aimed to determine how AT₂R activation modulates cellular metabolism and to identify pathways relevant to its tissue-protective actions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>3T3-L1 adipocytes, endothelial cells, and renal proximal tubular epithelial cells were treated with the specific AT₂R agonist Compound 21 (C21). Targeted liquid chromatography–tandem mass spectrometry was used to quantify amino acids and metabolites involved in energy metabolism and redox homeostasis. Functional analyses included nitrate/nitrite determination and cystathionine β-synthase (CBS) activity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compound 21 induced shared and cell type-specific metabolic changes. Arginine, citrulline, glucose, and glyceraldehyde 3-phosphate increased consistently across all cell types, whereas citrate decreased. Sulfur-containing metabolites and glutathione-related intermediates increased predominantly in adipocytes and renal cells. Pathway analysis highlighted three metabolic axes affected by C21: arginine biosynthesis, central carbon metabolism, and amino acid-linked redox pathways. Functionally, C21 increased nitrate/nitrite accumulation in BAECs and CBS activity in RPTECs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Treatment with C21 was associated with a conserved metabolic signature across adipocytes, renal epithelial cells, and endothelial cells involving arginine biosynthesis, central carbon metabolism, and amino acid-linked redox homeostasis. While the response differed among cell types, coordinated changes in arginine, citrulline, glucose, glyceraldehyde 3-phosphate, citrate, and GSH-related metabolites suggest that AT₂R signaling is associated with cellular pathways involved in nitric oxide metabolism, energy metabolism, and redox homeostasis. Increased NOx production in BAECs and CBS activity in RPTECs support the cell type-specific metabolic effects of C21.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 11","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149028029","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":"Regional Specialization of Electrolyte Transport Along the Trachea","authors":"Vazhaikkurichi M. Rajendran,&nbsp;Joshua Cornman-Homonoff,&nbsp;Geoffrey I. Sandle","doi":"10.1111/apha.70319","DOIUrl":"10.1111/apha.70319","url":null,"abstract":"&lt;p&gt;It is easy to view the airways simply as a route allowing air to move between the external environment and the gas-exchanging regions of the lungs. However, airway epithelial function is essential for pulmonary defense. Through coordinated ion transport, fluid and mucus secretion, and ciliary activity, airway epithelial cells regulate airway surface liquid composition and support mucociliary clearance, one of the respiratory system's most important defense mechanisms [&lt;span&gt;1, 2&lt;/span&gt;]. Considerable attention has been devoted to identifying transport proteins that mediate these processes. Much less is known about how epithelial transport processes are spatially organized along the proximal–distal axis of the airways. In this issue of &lt;i&gt;Acta Physiologica&lt;/i&gt;, Apablaza et al. provide compelling evidence that the mouse trachea is functionally compartmentalized, with proximal and distal regions exhibiting distinct patterns of ion transport and different responses to inflammatory stimuli [&lt;span&gt;3&lt;/span&gt;]. Their study challenges the common assumption that the tracheal epithelium functions as a homogeneous tissue and highlights the importance of anatomical location when interpreting the electrophysiological/ion transport properties of airway epithelia.&lt;/p&gt;&lt;p&gt;Using customized Ussing chambers to facilitate paired analysis of proximal and distal segments from the same trachea, the authors identified striking regional differences in both basal and stimulated ion transport [&lt;span&gt;3&lt;/span&gt;]. Distal trachea exhibited greater electrogenic Na&lt;sup&gt;+&lt;/sup&gt; absorption, whereas proximal trachea displayed stronger secretory responses to forskolin and succinate (Figure 1). Thus, different regions of the trachea are optimized for distinct physiological functions, which suggests that spatial organization contributes substantially to overall airway homeostasis. Importantly, the study goes beyond simple physiological characterization and begins to define the transport mechanisms underlying this regional differentiation. Functional analyses revealed regional differences in the contribution of electrogenic Na&lt;sup&gt;+&lt;/sup&gt;-HCO&lt;sub&gt;3&lt;/sub&gt;&lt;sup&gt;−&lt;/sup&gt; cotransporter-1 (NBCe1)-dependent HCO&lt;sub&gt;3&lt;/sub&gt;&lt;sup&gt;−&lt;/sup&gt; transport, TMEM16A-mediated Cl&lt;sup&gt;−&lt;/sup&gt; secretion, and Na&lt;sup&gt;+&lt;/sup&gt;-K&lt;sup&gt;+&lt;/sup&gt;-2Cl&lt;sup&gt;−&lt;/sup&gt; co-transporter-1 (NKCC1)-dependent anion transport [&lt;span&gt;3-6&lt;/span&gt;]. Immunolocalization studies identified distinct patterns of NKCC1 expression along the tracheal axis, with prominent staining in proximal submucosal glands and abundant NKCC1-positive epithelial cells distally. These structural observations provide an anatomical framework for understanding the physiological heterogeneity observed in electrophysiological recordings.&lt;/p&gt;&lt;p&gt;The work of Apablaza et al. also explains a long-standing observation familiar to many investigators working with airway epithelia. Responses to amiloride, commonly used to assess epithelial Na&lt;sup&gt;+&lt;/sup&gt; channel (ENaC)-mediat","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 10","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70319","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023280","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":"Bridging Disciplines: Translational Science as a Missing Link in Climate Health Research","authors":"Gabriel D. Rodrigues,&nbsp;Pedro Paulo S. Soares,&nbsp;Andreza P. Rodrigues,&nbsp;Pablo Pandolfo,&nbsp;Renata Libonati","doi":"10.1111/apha.70316","DOIUrl":"10.1111/apha.70316","url":null,"abstract":"","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 10","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149011708","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":"AS160 At the Crossroads of Nutrient Handling and Mitochondrial Quality Control in Pancreatic β-Cells","authors":"Emmanuel Ampofo,&nbsp;Leticia Prates Roma","doi":"10.1111/apha.70313","DOIUrl":"10.1111/apha.70313","url":null,"abstract":"&lt;p&gt;Pancreatic β-cells face an unusual metabolic challenge. Their physiological function requires mitochondria to constantly translate changes in nutrient availability into signals that control insulin secretion, while at the same time maintaining their integrity over decades. In a recent study in Acta Physiologica, Chen and colleagues [&lt;span&gt;1&lt;/span&gt;] identify a new player in this process: the Rab GTPase-activating protein AS160 (TBC1D4 in humans). Best known as a downstream target of insulin-Akt signaling that controls glucose transporter trafficking, AS160 is now proposed to also protect β-cells through a mechanism involving HSPA8, mitophagy and mitochondrial homeostasis.&lt;/p&gt;&lt;p&gt;AS160 is expressed in human and mouse β-cells, where glucose stimulates its phosphorylation, and loss of AS160 alters glucose-stimulated insulin secretion, proliferation and survival [&lt;span&gt;2&lt;/span&gt;]. Chen et al. [&lt;span&gt;1&lt;/span&gt;] now extend these observations by showing that AS160 expression is reduced in pancreatic islets from several hyperglycaemic mouse models. Moreover, increasing AS160 in β-cells attenuated streptozotocin (STZ)-induced hyperglycemia, increased circulating insulin and preserved islet area [&lt;span&gt;1&lt;/span&gt;]. These findings suggest that AS160 has a role in β-cells that goes beyond membrane trafficking (Figure 1).&lt;/p&gt;&lt;p&gt;This interpretation is consistent with the central role of mitochondria in β-cell physiology. Mitochondria are not simply ATP-producing organelles in β-cells, but a core part of the glucose-sensing machinery, and their metabolism, structure and dynamics are tightly linked to insulin secretion [&lt;span&gt;3, 4&lt;/span&gt;]. Mitochondrial dysfunction, however, does not necessarily lead to β-cell failure: islets can undergo substantial metabolic and structural adaptation that preserves insulin secretion despite underlying mitochondrial defects [&lt;span&gt;5&lt;/span&gt;]. Accordingly, β-cell resilience may depend not just on how much mitochondrial dysfunction occurs, but on the cell's capacity to remodel and maintain its mitochondrial network under stress. The findings of Chen et al. [&lt;span&gt;1&lt;/span&gt;] raise the possibility that AS160 contributes to this adaptive capacity.&lt;/p&gt;&lt;p&gt;Indeed, AS160 overexpression increased ATP content, mitochondrial respiration, mitochondrial membrane potential and mitochondrial abundance, while AS160 depletion reduced glucose uptake and ATP production [&lt;span&gt;1&lt;/span&gt;]. This raises the question of whether AS160 acts directly on mitochondria, or whether part of the mitochondrial phenotype is a downstream effect of changes in glucose handling. The authors also show that AS160 regulates GLUT2 distribution, and blocking glucose metabolism with 2-deoxyglucose reduced several effects of AS160 overexpression (Figure 1). These findings link nutrient flux to mitochondrial adaptation but do not establish a direct mitochondrial action of AS160. Determining whether AS160 acts directly on mitochondria therefore remains an important question.&lt;/p&gt;&lt;p&gt;A","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"242 10","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.70313","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149011651","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}