Acta Physiologica最新文献

{"title":"Time-dependent reduction in oxidative capacity among cultured myotubes from spinal cord injured individuals","authors":"Stanislava Stevanovic,&nbsp;Andrea Dalmao-Fernandez,&nbsp;Derya Mohamed,&nbsp;Tuula A. Nyman,&nbsp;Emil Kostovski,&nbsp;Per Ole Iversen,&nbsp;Mladen Savikj,&nbsp;Natasa Nikolic,&nbsp;Arild C. Rustan,&nbsp;G. Hege Thoresen,&nbsp;Eili T. Kase","doi":"10.1111/apha.14156","DOIUrl":"10.1111/apha.14156","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Skeletal muscle adapts in reaction to contractile activity to efficiently utilize energy substrates, primarily glucose and free fatty acids (FA). Inactivity leads to atrophy and a change in energy utilization in individuals with spinal cord injury (SCI). The present study aimed to characterize possible inactivity-related differences in the energy metabolism between skeletal muscle cells cultured from satellite cells isolated 1- and 12-months post-SCI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To characterize inactivity-related disturbances in spinal cord injury, we studied skeletal muscle cells isolated from SCI subjects. Cell cultures were established from biopsy samples from <i>musculus vastus lateralis</i> from subjects with SCI 1 and 12 months after the injury. The myoblasts were proliferated and differentiated into myotubes before fatty acid and glucose metabolism were assessed and gene and protein expressions were measured.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The results showed that glucose uptake was increased, while oleic acid oxidation was reduced at 12 months compared to 1 month. mRNA expressions of <i>PPARGC1α</i>, the master regulator of mitochondrial biogenesis, and <i>MYH2</i>, a determinant of muscle fiber type, were significantly reduced at 12 months. Proteomic analysis showed reduced expression of several mitochondrial proteins.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In conclusion, skeletal muscle cells isolated from immobilized subjects 12 months compared to 1 month after SCI showed reduced fatty acid metabolism and reduced expression of mitochondrial proteins, indicating an increased loss of oxidative capacity with time after injury.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 7","pages":""},"PeriodicalIF":6.3,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14156","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140848906","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":"Regulation of placental amino acid transport in health and disease","authors":"Hiroshi Shimada,&nbsp;Theresa L. Powell,&nbsp;Thomas Jansson","doi":"10.1111/apha.14157","DOIUrl":"10.1111/apha.14157","url":null,"abstract":"<p>Abnormal fetal growth, i.e., intrauterine growth restriction (IUGR) or fetal growth restriction (FGR) and fetal overgrowth, is associated with increased perinatal morbidity and mortality and is strongly linked to the development of metabolic and cardiovascular disease in childhood and later in life. Emerging evidence suggests that changes in placental amino acid transport may contribute to abnormal fetal growth. This review is focused on amino acid transport in the human placenta, however, relevant animal models will be discussed to add mechanistic insights. At least 25 distinct amino acid transporters with different characteristics and substrate preferences have been identified in the human placenta. Of these, System A, transporting neutral nonessential amino acids, and System L, mediating the transport of essential amino acids, have been studied in some detail. Importantly, decreased placental Systems A and L transporter activity is strongly associated with IUGR and increased placental activity of these two amino acid transporters has been linked to fetal overgrowth in human pregnancy. An array of factors in the maternal circulation, including insulin, IGF-1, and adiponectin, and placental signaling pathways such as mTOR, have been identified as key regulators of placental Systems A and L. Studies using trophoblast-specific gene targeting in mice have provided compelling evidence that changes in placental Systems A and L are mechanistically linked to altered fetal growth. It is possible that targeting specific placental amino acid transporters or their upstream regulators represents a novel intervention to alleviate the short- and long-term consequences of abnormal fetal growth in the future.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 7","pages":""},"PeriodicalIF":6.3,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140848324","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":"Effects of thiazides and new findings on kidney stones and dysglycemic side effects","authors":"Matteo Bargagli,&nbsp;Manuel A. Anderegg,&nbsp;Daniel G. Fuster","doi":"10.1111/apha.14155","DOIUrl":"10.1111/apha.14155","url":null,"abstract":"<p>Thiazide and thiazide-like diuretics (thiazides) belong to the most frequently prescribed drugs worldwide. By virtue of their natriuretic and vasodilating properties, thiazides effectively lower blood pressure and prevent adverse cardiovascular outcomes. In addition, through their unique characteristic of reducing urine calcium, thiazides are also widely employed for the prevention of kidney stone recurrence and reduction of bone fracture risk. Since their introduction into clinical medicine in the early 1960s, thiazides have been recognized for their association with metabolic side effects, particularly impaired glucose tolerance, and new-onset diabetes mellitus. Numerous hypotheses have been advanced to explain thiazide-induced glucose intolerance, yet underlying mechanisms remain poorly defined. Regrettably, the lack of understanding and unpredictability of these side effects has prompted numerous physicians to refrain from prescribing these effective, inexpensive, and widely accessible drugs. In this review, we outline the pharmacology and mechanism of action of thiazides, highlight recent advances in the understanding of thiazide-induced glucose intolerance, and provide an up-to-date discussion on the role of thiazides in kidney stone prevention.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 7","pages":""},"PeriodicalIF":6.3,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14155","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140834350","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":"Current insights into the Pathophysiology of kidney diseases","authors":"Anika Westphal","doi":"10.1111/apha.14158","DOIUrl":"10.1111/apha.14158","url":null,"abstract":"&lt;p&gt;Chronic kidney disease (CKD) affects 700–800 million humans per year.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Damage to the kidney is often recognized late, although early diagnosis is essential for successful treatment. While acute kidney injury can often be effectively managed, CKD poses a challenge due to irreversible structural damage, compromising intrinsic kidney functions such as regulation of fluid, electrolyte, and acid–base balance, and the release of hormones into the blood, for example, renin and erythropoietin (Epo). The decrease in the glomerular filtration rate (GFR) and the increase in albumin in the urine are the most important markers in the diagnosis of kidney diseases. This article presents novel findings on kidney diseases, potential approaches for future therapies and new impacts in preventing and treating different stages of renal diseases, recently published in &lt;i&gt;Acta Physiologica&lt;/i&gt;.&lt;/p&gt;&lt;p&gt;Early diagnosis of acute kidney injury (AKI) is of high importance for an adequate treatment. However, revealing early events in AKI is challenging, due to the absence of clear symptoms. Several urine- or blood-based markers for renal injury, fibrosis etc. have been suggested, with varying outcomes. In most forms of AKI, renal tissue hypoxia is an early marker. Hypoxia of the kidney tissue is also involved in the development of chronic and diabetic kidney disease. Kidney hypoxia often comes along with changes in kidney size. Cantow et al. analyzed in a magnetic resonance imaging (MRI)-based approach the connection between kidney size and renal tissue hypoxia. To achieve this, they used different interventions impairing renal tissue oxygenation, for example, occlusions and hypoxemia. MRI markers, kidney size, and their interactions were analyzed. In summary, observation of kidney size enables the interpretation of pathophysiological changes in kidney oxygenation. They conclude that monitoring of kidney size should always accompany MRI oximetry to gain essential information about renal disease levels, especially in acute changes in renal tissue oxygenation in AKI and its progression to CKD.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Betrie et al. and Xu et al. focus on exploring preventive measures against AKI in ovine and rat models. Half of the patients with sepsis develop AKI and thereby have a higher morbidity and mortality. In ovine sepsis, hypoxia and renal medullary hypoperfusion is often followed by AKI, probably due to inflammation and oxidative stress. So far, there is a lack of specific renal-protective therapies available that focuses on the reduction of inflammation and the increased bioavailability of reactive oxygen and nitrogen species that appear in the kidneys. Betrie et al. investigated a possible protective effect of tempol on the development of AKI following sepsis. Tempol is a synthetic heterocyclic nitroxide that has a positive effect on reducing oxidative stress, increasing the bioavailability of nitric oxide and inhibiting inflammation","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 7","pages":""},"PeriodicalIF":6.3,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14158","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140834351","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":"Mechanosensing by Piezo1 and its implications in the kidney","authors":"Xi Yuan,&nbsp;Xiaoduo Zhao,&nbsp;Weidong Wang,&nbsp;Chunling Li","doi":"10.1111/apha.14152","DOIUrl":"10.1111/apha.14152","url":null,"abstract":"<p>Piezo1 is an essential mechanosensitive transduction ion channel in mammals. Its unique structure makes it capable of converting mechanical cues into electrical and biological signals, modulating biological and (patho)physiological processes in a wide variety of cells. There is increasing evidence demonstrating that the piezo1 channel plays a vital role in renal physiology and disease conditions. This review summarizes the current evidence on the structure and properties of Piezo1, gating modulation, and pharmacological characteristics, with special focus on the distribution and (patho)physiological significance of Piezo1 in the kidney, which may provide insights into potential treatment targets for renal diseases involving this ion channel.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 6","pages":""},"PeriodicalIF":6.3,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140834403","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":"Landscape of transcriptome-wide m6A modification in diabetic liver reveals rewiring of PI3K-Akt signaling after physical exercise","authors":"Cong Chen,&nbsp;Cai Jiang,&nbsp;Ting Lin,&nbsp;Yue Hu,&nbsp;Huijuan Wu,&nbsp;Qing Xiang,&nbsp;Minguang Yang,&nbsp;Sinuo Wang,&nbsp;Xiao Han,&nbsp;Jing Tao","doi":"10.1111/apha.14154","DOIUrl":"10.1111/apha.14154","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Type 2 diabetes mellitus (T2DM) is one of the most common diseases, and epigenetic modification N6-methyladenosine (m⁶A) is essential for transcriptional modulation involved in its development. However, the precise role and landscape of transcriptome-wide m⁶A alterations in molecular adaptations after physical exercise have yet to be fully elucidated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Four-week-old male C57BL/6J mice received a high-fat diet (HFD) for 12 weeks to establish a diabetic state, and HFD mice were simultaneously subjected to physical exercise (HFD + EX). The hepatic RNA m⁶A methylome was examined, the conjoint MeRIP-seq and RNA-seq was performed, and the exercise-modulated genes were confirmed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Physical exercise significantly ameliorates liver metabolic disorder and triggers a dynamic change in hepatic RNA m⁶A. By analyzing the distribution of m⁶A in transcriptomes, an abundance of m⁶A throughout mRNA transcripts and a pattern of conserved m⁶A after physical exercise was identified. It is noteworthy that conjoint MeRIP-seq and RNA-seq data revealed that both differentially methylated genes and differentially expressed genes were enriched in all stages of the PI3K-Akt signaling pathway, in particular the upstream nodes of this pathway, which are considered a valuable therapeutic target for T2DM. Moreover, in vivo and in vitro analyses showed that exercise-mediated methyltransferase Rbm15 positively regulated the expression of two upstream genes (Itga3 and Fgf21) in an m⁶A-dependent manner.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings highlight the pivotal role of the exercise-induced m⁶A epigenetic network and contribute insights into the intricate epigenetic mechanism underlying insulin signaling.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 6","pages":""},"PeriodicalIF":6.3,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14154","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140834355","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":"Unlocking mitochondrial drug targets: The importance of mitochondrial transport proteins","authors":"Charlotte A. Hoogstraten,&nbsp;Tom J. J. Schirris,&nbsp;Frans G. M. Russel","doi":"10.1111/apha.14150","DOIUrl":"10.1111/apha.14150","url":null,"abstract":"<p>A disturbed mitochondrial function contributes to the pathology of many common diseases. These organelles are therefore important therapeutic targets. On the contrary, many adverse effects of drugs can be explained by a mitochondrial off-target effect, in particular, due to an interaction with carrier proteins in the inner membrane. Yet this class of transport proteins remains underappreciated and understudied. The aim of this review is to provide a deeper understanding of the role of mitochondrial carriers in health and disease and their significance as drug targets. We present literature-based evidence that mitochondrial carrier proteins are associated with prevalent diseases and emphasize their potential as drug (off-)target sites by summarizing known mitochondrial drug–transporter interactions. Studying these carriers will enhance our knowledge of mitochondrial drug on- and off-targets and provide opportunities to further improve the efficacy and safety of drugs.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 6","pages":""},"PeriodicalIF":6.3,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14150","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140652303","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":"A potent and selective activator of large-conductance Ca2+-activated K+ channels induces preservation of mitochondrial function after hypoxia and reoxygenation by handling of calcium and transmembrane potential","authors":"Itanna Isis Araujo de Souza,&nbsp;Thais da Silva Barenco,&nbsp;Maria Eduarda Maciel Fernandes Pavarino,&nbsp;Marcos Tadeu Couto,&nbsp;Gabriel Oliveira de Resende,&nbsp;Dahienne Ferreira de Oliveira,&nbsp;Cristiano Gonsalves Ponte,&nbsp;José Hamilton Matheus Nascimento,&nbsp;Leonardo Maciel","doi":"10.1111/apha.14151","DOIUrl":"10.1111/apha.14151","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Ischaemic heart disease remains a significant cause of mortality globally. A pharmacological agent that protects cardiac mitochondria against oxygen deprivation injuries is welcome in therapy against acute myocardial infarction. Here, we evaluate the effect of large-conductance Ca²⁺-activated K⁺ channels (BKCa) activator, Compound Z, in isolated mitochondria under hypoxia and reoxygenation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Mitochondria from mice hearts were obtained by differential centrifugation. The isolated mitochondria were incubated with a BKCa channel activator, Compound Z, and subjected to normoxia or hypoxia/reoxygenation. Mitochondrial function was evaluated by measurement of O₂ consumption in the complexes I, II, and IV in the respiratory states 1, 2, 3, and by maximal uncoupled O₂ uptake, ATP production, ROS production, transmembrane potential, and calcium retention capacity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Incubation of isolated mitochondria with Compound Z under normoxia conditions reduced the mitochondrial functions and induced the production of a significant amount of ROS. However, under hypoxia/reoxygenation, the Compound Z prevented a profound reduction in mitochondrial functions, including reducing ROS production over the hypoxia/reoxygenation group. Furthermore, hypoxia/reoxygenation induced a large mitochondria depolarization, which Compound Z incubation prevented, but, even so, Compound Z created a small depolarization. The mitochondrial calcium uptake was prevented by the BKCa activator, extruding the mitochondrial calcium present before Compound Z incubation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The Compound Z acts as a mitochondrial BKCa channel activator and can protect mitochondria function against hypoxia/reoxygenation injury, by handling mitochondrial calcium and transmembrane potential.</p>\u0000 </section>\u0000 </div>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 6","pages":""},"PeriodicalIF":6.3,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140810621","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 guidelines to uncover the physiology of extracellular vesicles","authors":"Didde R. Hansen,&nbsp;Per Svenningsen","doi":"10.1111/apha.14153","DOIUrl":"10.1111/apha.14153","url":null,"abstract":"&lt;p&gt;Extracellular vesicles (EVs)—nanosized membrane-enclosed particles containing cellular RNA, lipids, and proteins—are secreted from cells into body fluids such as urine and plasma. The EVs provide exciting opportunities to understand human and animal physiology in that they can be used as liquid biopsies to gain mechanistic insight into complex conditions, such as hypertension.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Moreover, EVs may serve as vehicles for intercellular communication, potentially adding new layers to the understanding of physiology. However, challenges to purify, characterize, and determine, for example, the intercellular transfer of EVs, have remained a hurdle to realizing the potential of EVs. To address these challenges, the International Society of Extracellular Vesicles (ISEV) has published the “Minimal Information for Studies of Extracellular Vesicles” (MISEV) as a guideline for best practices in EV research. An updated version—MISEV2023&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt;—has been published and contains essential information on the advantages and limitations of current methods to study EV biology. This article will highlight new additions to the MISEV2023 critical for determining the physiological role of EVs.&lt;/p&gt;&lt;p&gt;The current MISEV2023 guidelines stand on the shoulders of the two previous versions: MISEV2014 and MISEV2018. The MISEV2023 document was updated by expert task forces within the specific sections and through online feedback from over 1000 ISEV members. This community effort has resulted in a rich source of detailed and comprehensive information on EVs and important sample-specific recommendations and caveats for collecting, preprocessing, and characterizing EVs isolated from biofluids and tissue samples. MISEV2023 also contains updated nomenclature and characterization sections to integrate the greater complexity and diversity of EVs and nonvesicular extracellular particles, such as exomeres, uncovered by recent EV research. Importantly, MISEV2023 values transparency highly and should be considered a guide to rigorous and reproducible EV science.&lt;/p&gt;&lt;p&gt;A significant challenge for studying EV biology in living organisms is the low EV concentration in body fluids. For example, the EV concentration in human blood—one of the most studied body fluids—is seven orders of magnitude lower than albumin and approximately one-tenth of the fasting insulin level (Figure 1). In contrast to hormones and plasma proteins, often secreted from a small number of cells,&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; EVs in body fluids are derived from various cell types, and ~90% of the circulating plasma EVs are derived from blood cells.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; The low abundance challenges not only cell type-specific EV cargo analyses but also the determination of how they are taken up by other cells and their biodistribution, for example, whether plasma EVs are filtered into the urine.&lt;/p&gt;&lt;p&gt;The EV biodistribution has been primarily assessed by bolus injection of EVs isolat","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 6","pages":""},"PeriodicalIF":6.3,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14153","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140654699","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":"Unique features of β-cell metabolism are lost in type 2 diabetes","authors":"Felipe Muñoz,&nbsp;Malin Fex,&nbsp;Thomas Moritz,&nbsp;Hindrik Mulder,&nbsp;Luis Rodrigo Cataldo","doi":"10.1111/apha.14148","DOIUrl":"10.1111/apha.14148","url":null,"abstract":"<p>Pancreatic β cells play an essential role in the control of systemic glucose homeostasis as they sense blood glucose levels and respond by secreting insulin. Upon stimulating glucose uptake in insulin-sensitive tissues post-prandially, this anabolic hormone restores blood glucose levels to pre-prandial levels. Maintaining physiological glucose levels thus relies on proper β-cell function. To fulfill this highly specialized nutrient sensor role, β cells have evolved a unique genetic program that shapes its distinct cellular metabolism. In this review, the unique genetic and metabolic features of β cells will be outlined, including their alterations in type 2 diabetes (T2D). β cells selectively express a set of genes in a cell type-specific manner; for instance, the glucose activating hexokinase IV enzyme or Glucokinase (<i>GCK</i>), whereas other genes are selectively “disallowed”, including lactate dehydrogenase A (<i>LDHA</i>) and monocarboxylate transporter 1 (<i>MCT1</i>). This selective gene program equips β cells with a unique metabolic apparatus to ensure that nutrient metabolism is coupled to appropriate insulin secretion, thereby avoiding hyperglycemia, as well as life-threatening hypoglycemia. Unlike most cell types, β cells exhibit specialized bioenergetic features, including supply-driven rather than demand-driven metabolism and a high basal mitochondrial proton leak respiration. The understanding of these unique genetically programmed metabolic features and their alterations that lead to β-cell dysfunction is crucial for a comprehensive understanding of T2D pathophysiology and the development of innovative therapeutic approaches for T2D patients.</p>","PeriodicalId":107,"journal":{"name":"Acta Physiologica","volume":"240 6","pages":""},"PeriodicalIF":6.3,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.14148","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140662093","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}