Nutrition and metabolism are fundamental to understanding the physiological basis of the most prevalent diseases currently in society. Cardiovascular disease, type 2 diabetes and even dementia have a metabolic underpinning (Reaven, 1988; Ferrari & Sorbi, 2021). Diet-related chronic diseases account for at least 9% of the National Health Service budget in the UK; which equates to at least £12 billion per annum (DEFRA, 2014). In addition to health, nutrition is fundamental to optimizing human performance via the provision of chemical energy in addition to modulating adaptation to exercise (Burke & Hawley, 2018). Therefore, understanding the physiology of nutrition can aid in reducing disease burden and extending the limits of human performance. ‘Novel dietary approaches to appetite regulation, health and performance’ was the title of a Highlighted Symposium originally due to be delivered in 2020, but delayed by a year and delivered online as part of the 2021 American College of Sports Medicine Annual meeting, and was supported by The Journal of Physiology. The aim of this symposium was for the four speakers to cover new ways in which nutrition can be used to regulate appetite and improve human health and performance. An emerging theme was the role of nutrient timing, possibly reflecting the increasing focus on when we eat in addition to what we eat. Smith and Betts (2022) provide an overarching review of how circadian rhythms relate to nutrition, physical activity and light exposure. Metabolic responses to food ingestion are dependent on the time of day. Glucose and triacylglycerol concentrations, for example, typically show larger postprandial increases in the evening versus the morning (Smith & Betts, 2022). These responses are likely mediated by diurnal rhythms in β-cell function, insulin secretion, clearance and sensitivity, very low density lipoprotein secretion and intestinal triacylglycerol absorption (Smith & Betts, 2022). With respect to appetite regulation, hunger ratings during constant routine and forced desynchrony protocols are commonly reported to be lowest in the morning and peak in the evening, which may partly be regulated by variation in gut peptide concentrations (Templeman et al. 2021b). Given that nutrition is a key signal for biological rhythms, the role of manipulating nutrient timing on physiological responses was discussed. Whilst continuous 24 h feeding appears to disrupt some aspects of hormonal regulation (Gonzalez et al. 2020), extending the overnight fast (i.e. skipping breakfast), can increase the glycaemic responses to lunch (the contrasting response to breakfast consumption is commonly referred to as the second-meal effect) (Gonzalez et al. 2013). When breakfast skipping is extended over 6 weeks, there is evidence of more stable interstitial glucose concentrations and altered mRNA expression in adipose tissue (Betts et al. 2014; Gonzalez et al. 2018). Extending fasting periods to 24 h with a form of intermittent fa
{"title":"Novel dietary approaches to appetite regulation, health and performance","authors":"J. Gonzalez","doi":"10.1113/JP282727","DOIUrl":"https://doi.org/10.1113/JP282727","url":null,"abstract":"Nutrition and metabolism are fundamental to understanding the physiological basis of the most prevalent diseases currently in society. Cardiovascular disease, type 2 diabetes and even dementia have a metabolic underpinning (Reaven, 1988; Ferrari & Sorbi, 2021). Diet-related chronic diseases account for at least 9% of the National Health Service budget in the UK; which equates to at least £12 billion per annum (DEFRA, 2014). In addition to health, nutrition is fundamental to optimizing human performance via the provision of chemical energy in addition to modulating adaptation to exercise (Burke & Hawley, 2018). Therefore, understanding the physiology of nutrition can aid in reducing disease burden and extending the limits of human performance. ‘Novel dietary approaches to appetite regulation, health and performance’ was the title of a Highlighted Symposium originally due to be delivered in 2020, but delayed by a year and delivered online as part of the 2021 American College of Sports Medicine Annual meeting, and was supported by The Journal of Physiology. The aim of this symposium was for the four speakers to cover new ways in which nutrition can be used to regulate appetite and improve human health and performance. An emerging theme was the role of nutrient timing, possibly reflecting the increasing focus on when we eat in addition to what we eat. Smith and Betts (2022) provide an overarching review of how circadian rhythms relate to nutrition, physical activity and light exposure. Metabolic responses to food ingestion are dependent on the time of day. Glucose and triacylglycerol concentrations, for example, typically show larger postprandial increases in the evening versus the morning (Smith & Betts, 2022). These responses are likely mediated by diurnal rhythms in β-cell function, insulin secretion, clearance and sensitivity, very low density lipoprotein secretion and intestinal triacylglycerol absorption (Smith & Betts, 2022). With respect to appetite regulation, hunger ratings during constant routine and forced desynchrony protocols are commonly reported to be lowest in the morning and peak in the evening, which may partly be regulated by variation in gut peptide concentrations (Templeman et al. 2021b). Given that nutrition is a key signal for biological rhythms, the role of manipulating nutrient timing on physiological responses was discussed. Whilst continuous 24 h feeding appears to disrupt some aspects of hormonal regulation (Gonzalez et al. 2020), extending the overnight fast (i.e. skipping breakfast), can increase the glycaemic responses to lunch (the contrasting response to breakfast consumption is commonly referred to as the second-meal effect) (Gonzalez et al. 2013). When breakfast skipping is extended over 6 weeks, there is evidence of more stable interstitial glucose concentrations and altered mRNA expression in adipose tissue (Betts et al. 2014; Gonzalez et al. 2018). Extending fasting periods to 24 h with a form of intermittent fa","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89362804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D. Thijssen, L. Uthman, Yasina B. Somani, N. van Royen
Regular exercise training has potent and powerful protective effects against the development of cardiovascular disease. These cardioprotective effects of regular exercise training are partly explained through the effects of exercise on traditional cardiovascular risk factors and improvement in cardiac and vascular health, which take several weeks to months to develop. This review focuses on the observation that single bouts of exercise may also possess an underrecognized, clinically useful form of immediate cardioprotection. Studies, performed in both animals and humans, demonstrate that single or short‐term exercise‐induced protection (SEP) attenuates the magnitude of cardiac and/or vascular damage in response to prolonged ischaemia and reperfusion injury. This review highlights preclinical evidence supporting the hypothesis that SEP activates multiple pathways to confer immediate protection against ischaemic events, reduce the severity of potentially lethal ischaemic myocardial injury, and therefore act as a physiological first line of defence against injury. Given the fact that the extent of SEP could be modulated by exercise‐related and subject‐related factors, it is important to recognize and consider these factors to optimize future clinical implications of SEP. This review also summarizes potential effector signalling pathways (i.e. communication between exercising muscles to vascular/cardiac tissue) and intracellular pathways (i.e. reducing tissue damage) that ultimately confer protection against cardiac and vascular injury. Finally, we discuss potential future directions for designing adequate human and animal studies that will support developing effective SEP strategies for the (multi‐)diseased and aged individual.
{"title":"Short‐term exercise‐induced protection of cardiovascular function and health: why and how fast does the heart benefit from exercise?","authors":"D. Thijssen, L. Uthman, Yasina B. Somani, N. van Royen","doi":"10.1113/JP282000","DOIUrl":"https://doi.org/10.1113/JP282000","url":null,"abstract":"Regular exercise training has potent and powerful protective effects against the development of cardiovascular disease. These cardioprotective effects of regular exercise training are partly explained through the effects of exercise on traditional cardiovascular risk factors and improvement in cardiac and vascular health, which take several weeks to months to develop. This review focuses on the observation that single bouts of exercise may also possess an underrecognized, clinically useful form of immediate cardioprotection. Studies, performed in both animals and humans, demonstrate that single or short‐term exercise‐induced protection (SEP) attenuates the magnitude of cardiac and/or vascular damage in response to prolonged ischaemia and reperfusion injury. This review highlights preclinical evidence supporting the hypothesis that SEP activates multiple pathways to confer immediate protection against ischaemic events, reduce the severity of potentially lethal ischaemic myocardial injury, and therefore act as a physiological first line of defence against injury. Given the fact that the extent of SEP could be modulated by exercise‐related and subject‐related factors, it is important to recognize and consider these factors to optimize future clinical implications of SEP. This review also summarizes potential effector signalling pathways (i.e. communication between exercising muscles to vascular/cardiac tissue) and intracellular pathways (i.e. reducing tissue damage) that ultimately confer protection against cardiac and vascular injury. Finally, we discuss potential future directions for designing adequate human and animal studies that will support developing effective SEP strategies for the (multi‐)diseased and aged individual.","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"1228 1","pages":"1339 - 1355"},"PeriodicalIF":0.0,"publicationDate":"2021-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85236955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-06-29DOI: 10.1113/jphysiol.1997.sp021990
D. Lipscombe, C. Toro
{"title":"Ion Channels","authors":"D. Lipscombe, C. Toro","doi":"10.1113/jphysiol.1997.sp021990","DOIUrl":"https://doi.org/10.1113/jphysiol.1997.sp021990","url":null,"abstract":"","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80845268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Keeping our lungs healthy is a challenging job as every breath we take exposes our airways to myriad pathogenic organisms. The conducting airways have evolved a sophisticated system that prevents this by first capturing the nasty bugs in a sea of mucus and then propelling the entrapped microorganisms upwards towards the mouth, where they are either swallowed or spat out. The removal of the bug-laden mucus by mucociliary clearance (MCC) is a key process and the first line of defence against inhaled pathogens (Saint-Criq & Gray, 2017). Reduction in MCC leads to airway disease such as cystic fibrosis (CF). Here, dysfunction in the apically located CFTR chloride channel causes a severe reduction in the airways’ surface hydration. This makes the mucus very sticky and difficult to move, resulting in MCC failure and eventual chronic lung-destroying infections. While CFTR is clearly essential for MCC, there are other chloride channels that provide a partial back-up to CFTR. The most well studied is the calcium-activated chloride channel (CaCC), which is switched on by a rise in cytosolic calcium, conventionally caused by G-protein-coupled receptor agonists such as nucleotides and acetylcholine (Saint-Criq & Gray, 2017). For many years the identity of the airway CaCC was unknown until three papers in 2008 discovered that the TMEM16A gene encodes a CaCC which is expressed in airway epithelial cells, as well as many other cell types (Kunzelmann et al. 2019). These papers were the catalyst that led to a much better understanding of how the channel works at an atomic level as well as furthering our understanding of the physiological function of TMEM16A in diverse tissues, including epithelial, sensory and muscle (Kunzelmann et al. 2019). Not surprisingly, scientists realised the potential of TMEM16A as a target for treating important human disease such as CF, asthma, hypertension and gastrointestinal motility disorders. Several groups have reported the identification of ‘specific’ small molecule activators and potentiators, as well as a plethora of putative inhibitors of TMEM16A (Kunzelmann et al. 2019). One such TMEM16A modulator, known as Eact, was identified by the Verkman group back in 2011. This compound was shown to stimulate TMEM16A without changing cytosolic calcium and therefore thought to be a bone fide TMEM16A activator. Since then, several groups have reported conflicting results, either that Eact failed to activate TMEM16A, or that it activated TMEM16A, but this was due to an Eact-induced increase in cytosolic calcium. The paper in this issue of The Journal of Physiology by Genovese et al. (2019) has shed new light on the ‘Eact/TMEM16A conundrum’, and provides a very nice physiological explanation for these apparent discrepancies. The authors found that the response to Eact was cell model dependent. In cell lines expressing TMEM16A, Eact activated the channel. However, in fully differentiated airway epithelial cultures, Eact failed to activate TM
气道中TRPV4的“生理”调节因子是什么?是否可以利用它来改善CFTR功能障碍疾病(如CF和慢性阻塞性肺疾病(COPD))的CFTR活性?此外，TRPV4和CFTR是否在其他上皮组织中共定位?这是一个有趣的观点，因为TRPV4在胃肠道和神经肌肉系统等其他组织中也引起了相当大的关注。最后，由于TMEM16A在体内具有许多重要的生理作用，因此确实需要找到一种特定的TMEM16A激活剂。在气道中，TMEM16A大部分位于粘液分泌细胞中(Genovese et al. 2019)，其表达与粘液细胞增生和粘液分泌随意相关。因此，特定的TMEM16A激活剂将是一个有价值的工具，有助于确定TMEM16A激活作为慢性气道疾病(如CF、COPD或哮喘)的新治疗方法是有益还是有害(Kunzelmann et al. 2019)。使用Genovese等人采用的多方法方法，并将这些方法与气道水化和MCC的功能读数相结合，应该能够回答这些重要问题。这些都是未来发展的迫切需要
{"title":"Location, location, location: lessons from airway epithelial anion channels","authors":"L. Delpiano, M. Gray","doi":"10.1113/JP279125","DOIUrl":"https://doi.org/10.1113/JP279125","url":null,"abstract":"Keeping our lungs healthy is a challenging job as every breath we take exposes our airways to myriad pathogenic organisms. The conducting airways have evolved a sophisticated system that prevents this by first capturing the nasty bugs in a sea of mucus and then propelling the entrapped microorganisms upwards towards the mouth, where they are either swallowed or spat out. The removal of the bug-laden mucus by mucociliary clearance (MCC) is a key process and the first line of defence against inhaled pathogens (Saint-Criq & Gray, 2017). Reduction in MCC leads to airway disease such as cystic fibrosis (CF). Here, dysfunction in the apically located CFTR chloride channel causes a severe reduction in the airways’ surface hydration. This makes the mucus very sticky and difficult to move, resulting in MCC failure and eventual chronic lung-destroying infections. While CFTR is clearly essential for MCC, there are other chloride channels that provide a partial back-up to CFTR. The most well studied is the calcium-activated chloride channel (CaCC), which is switched on by a rise in cytosolic calcium, conventionally caused by G-protein-coupled receptor agonists such as nucleotides and acetylcholine (Saint-Criq & Gray, 2017). For many years the identity of the airway CaCC was unknown until three papers in 2008 discovered that the TMEM16A gene encodes a CaCC which is expressed in airway epithelial cells, as well as many other cell types (Kunzelmann et al. 2019). These papers were the catalyst that led to a much better understanding of how the channel works at an atomic level as well as furthering our understanding of the physiological function of TMEM16A in diverse tissues, including epithelial, sensory and muscle (Kunzelmann et al. 2019). Not surprisingly, scientists realised the potential of TMEM16A as a target for treating important human disease such as CF, asthma, hypertension and gastrointestinal motility disorders. Several groups have reported the identification of ‘specific’ small molecule activators and potentiators, as well as a plethora of putative inhibitors of TMEM16A (Kunzelmann et al. 2019). One such TMEM16A modulator, known as Eact, was identified by the Verkman group back in 2011. This compound was shown to stimulate TMEM16A without changing cytosolic calcium and therefore thought to be a bone fide TMEM16A activator. Since then, several groups have reported conflicting results, either that Eact failed to activate TMEM16A, or that it activated TMEM16A, but this was due to an Eact-induced increase in cytosolic calcium. The paper in this issue of The Journal of Physiology by Genovese et al. (2019) has shed new light on the ‘Eact/TMEM16A conundrum’, and provides a very nice physiological explanation for these apparent discrepancies. The authors found that the response to Eact was cell model dependent. In cell lines expressing TMEM16A, Eact activated the channel. However, in fully differentiated airway epithelial cultures, Eact failed to activate TM","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"114 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82441497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Obesity and a sedentary lifestyle are major contributors to poor metabolic and vascular health. As such, there has been a focus towards understanding the mechanisms underlying improvements in health related to physical activity. However, there remains a need for strategies that encourage patients to perform exercise independently and outside of the laboratory-supervised research setting. Investigations into skeletal muscle microvasculature function can provide insight into the links between cardiovascular and metabolic health. Increased nitric oxide (NO) production via endothelial NO synthase (eNOS) promotes muscle capillary recruitment to increase insulin-stimulated glucose uptake (Vincent et al. 2004). However, the levels of bioavailable NO are reduced in obesity due to quenching by oxidants, such as superoxide. NADPH oxidase (NOX) complexes are predominant sources of superoxide in the endothelium of obese individuals; therefore, the relative activation of eNOS versus NOX may provide an indication of microvascular function. In a recent issue of The Journal of Physiology, Scott et al. (2019) investigated whether home-based exercise can mitigate insulin resistance and vascular dysfunction while eliminating potential barriers of exercise adherence, such as access to facilities. Thirty-two males and females (age 36 ± 10 years) with an elevated risk of developing cardiovascular disease (body mass index 34.3 ± 5 kg/m; V̇O2peak 24.6 5.7 ml/kg/min) performed 12 weeks of exercise training under one of the following conditions: home-based high-intensity interval training (Home-HIT; n = 9), laboratory-based supervised HIT (Lab-HIT; n = 10) or home-based moderate-intensity continuous training (Home-MICT; n = 13). The participants who performed home-based exercise were ‘virtually supervised’ using a heart rate monitor, and instructed to achieve 80% or 65% of predicted heart rate maximum (HRmax 220 – age) during the intervals or continuous exercise, respectively. The home-based and laboratory-supervised HIT exercise sessions consisted of 1-min bouts of exercise interspersed with 1 min of rest. The Home-MICT group was instructed to perform continuous exercise of either swimming, cycling or walking/running. Participants in each group trained three times per week. To monitor adherence to exercise prescription, HR data obtained from the HR monitors were automatically uploaded to a cloud storage site (www.flow.polar.com) after each session. Endothelial function and aortic stiffness were assessed via flow-mediated dilatation (FMD) and pulse wave velocity (PWV), respectively. Insulin sensitivity was measured using an oral glucose tolerance test (OGTT). Lastly, a resting muscle biopsy was collected to measure markers of metabolic and vascular function via immunofluorescence. The primary finding was that the improvements in endothelium-dependent dilatation, aortic stiffness and insulin sensitivity were comparable between home-based exercise groups and laboratory-supe
肥胖和久坐不动的生活方式是导致新陈代谢和血管健康不佳的主要原因。因此，人们一直致力于了解与体育活动有关的健康改善的潜在机制。然而，仍然需要一些策略来鼓励患者在实验室监督的研究环境之外独立地进行锻炼。对骨骼肌微血管功能的研究可以深入了解心血管和代谢健康之间的联系。通过内皮NO合成酶(eNOS)增加一氧化氮(NO)的产生，促进肌肉毛细血管募集，从而增加胰岛素刺激下的葡萄糖摄取(Vincent et al. 2004)。然而，由于氧化剂(如超氧化物)的猝灭，肥胖患者的生物可利用一氧化氮水平降低。NADPH氧化酶(NOX)复合物是肥胖个体内皮中超氧化物的主要来源;因此，eNOS与NOX的相对激活可能提供微血管功能的指示。在最近一期的《生理学杂志》(The Journal of Physiology)上，斯科特等人(2019)研究了在家锻炼是否能减轻胰岛素抵抗和血管功能障碍，同时消除坚持锻炼的潜在障碍，比如使用设施。心血管疾病风险增高的男女32人(年龄36±10岁)(体重指数34.3±5 kg/m;在以下条件之一下进行12周的运动训练:基于家庭的高强度间歇训练(Home-HIT;n = 9)，实验室监督HIT (Lab-HIT;n = 10)或以家庭为基础的中等强度连续训练(Home-MICT;N = 13)。在家锻炼的参与者使用心率监测器进行“虚拟监督”，并指示他们在间歇或连续锻炼期间分别达到预测心率最大值(HRmax 220 -年龄)的80%或65%。基于家庭和实验室监督的HIT锻炼包括1分钟的运动，穿插1分钟的休息。Home-MICT组被要求进行游泳、骑自行车或步行/跑步等连续运动。每组参与者每周训练三次。为了监测运动处方的依从性，从HR监测器获得的HR数据在每次锻炼后自动上传到云存储站点(www.flow.polar.com)。内皮功能和主动脉硬度分别通过血流介导扩张(FMD)和脉搏波速度(PWV)进行评估。采用口服葡萄糖耐量试验(OGTT)测定胰岛素敏感性。最后，收集静息肌肉活检，通过免疫荧光测量代谢和血管功能标志物。研究的主要发现是，在内皮依赖性扩张、主动脉僵硬和胰岛素敏感性方面的改善，在家庭锻炼组和实验室监督锻炼组之间是相当的。此外，无论运动组如何，骨骼肌微血管功能的改善都是相似的。值得注意的是，每组参与者也经历了伴随的V²o2峰值改善。这项研究的结果表明，进行高强度或中等强度的家庭运动是降低患心脏代谢疾病风险的有效策略。鉴于肥胖人群中HIT的可行性和实用性受到挑战，Scott等人(2019)证明，与在实验室监督的环境中执行HIT相比，在家中执行HIT可以获得类似的改善。
{"title":"Home exercise reduces cardiometabolic disease risk","authors":"Cesar A Meza","doi":"10.1113/JP278934","DOIUrl":"https://doi.org/10.1113/JP278934","url":null,"abstract":"Obesity and a sedentary lifestyle are major contributors to poor metabolic and vascular health. As such, there has been a focus towards understanding the mechanisms underlying improvements in health related to physical activity. However, there remains a need for strategies that encourage patients to perform exercise independently and outside of the laboratory-supervised research setting. Investigations into skeletal muscle microvasculature function can provide insight into the links between cardiovascular and metabolic health. Increased nitric oxide (NO) production via endothelial NO synthase (eNOS) promotes muscle capillary recruitment to increase insulin-stimulated glucose uptake (Vincent et al. 2004). However, the levels of bioavailable NO are reduced in obesity due to quenching by oxidants, such as superoxide. NADPH oxidase (NOX) complexes are predominant sources of superoxide in the endothelium of obese individuals; therefore, the relative activation of eNOS versus NOX may provide an indication of microvascular function. In a recent issue of The Journal of Physiology, Scott et al. (2019) investigated whether home-based exercise can mitigate insulin resistance and vascular dysfunction while eliminating potential barriers of exercise adherence, such as access to facilities. Thirty-two males and females (age 36 ± 10 years) with an elevated risk of developing cardiovascular disease (body mass index 34.3 ± 5 kg/m; V̇O2peak 24.6 5.7 ml/kg/min) performed 12 weeks of exercise training under one of the following conditions: home-based high-intensity interval training (Home-HIT; n = 9), laboratory-based supervised HIT (Lab-HIT; n = 10) or home-based moderate-intensity continuous training (Home-MICT; n = 13). The participants who performed home-based exercise were ‘virtually supervised’ using a heart rate monitor, and instructed to achieve 80% or 65% of predicted heart rate maximum (HRmax 220 – age) during the intervals or continuous exercise, respectively. The home-based and laboratory-supervised HIT exercise sessions consisted of 1-min bouts of exercise interspersed with 1 min of rest. The Home-MICT group was instructed to perform continuous exercise of either swimming, cycling or walking/running. Participants in each group trained three times per week. To monitor adherence to exercise prescription, HR data obtained from the HR monitors were automatically uploaded to a cloud storage site (www.flow.polar.com) after each session. Endothelial function and aortic stiffness were assessed via flow-mediated dilatation (FMD) and pulse wave velocity (PWV), respectively. Insulin sensitivity was measured using an oral glucose tolerance test (OGTT). Lastly, a resting muscle biopsy was collected to measure markers of metabolic and vascular function via immunofluorescence. The primary finding was that the improvements in endothelium-dependent dilatation, aortic stiffness and insulin sensitivity were comparable between home-based exercise groups and laboratory-supe","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"73 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89895318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Non-synergistic synergies of muscle activation: an apparent oxymoron Francesco Lacquaniti , Francesca Sylos-Labini and Myrka Zago Department of Systems Medicine and Center of Space BioMedicine of the University of Rome Tor Vergata, Rome, Italy Laboratory of Neuromotor Physiology of the IRCCS Santa Lucia Foundation, Rome, Italy Department of Civil Engineering and Computer Science Engineering and Centre of Space Biomedicine of the University of Rome Tor Vergata, Rome, Italy
{"title":"Non‐synergistic synergies of muscle activation: an apparent oxymoron","authors":"F. Lacquaniti, F. Sylos-Labini, M. Zago","doi":"10.1113/JP279111","DOIUrl":"https://doi.org/10.1113/JP279111","url":null,"abstract":"Non-synergistic synergies of muscle activation: an apparent oxymoron Francesco Lacquaniti , Francesca Sylos-Labini and Myrka Zago Department of Systems Medicine and Center of Space BioMedicine of the University of Rome Tor Vergata, Rome, Italy Laboratory of Neuromotor Physiology of the IRCCS Santa Lucia Foundation, Rome, Italy Department of Civil Engineering and Computer Science Engineering and Centre of Space Biomedicine of the University of Rome Tor Vergata, Rome, Italy","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77784197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
On 23 August 2019, science lost one of its great minds: Paul Michel Georges Remi Vanhoutte, born on 26 November 1940 in Merelbeke near Ghent in Belgium, unexpectedly died in Paris after he had suffered a fall 10 days earlier. He was ‘one of the fathers of vascular biology’ (Heistad, 2008) who contributed to and shaped our understanding of how vascular endothelial cells regulate blood flow under physiological conditions and in disease.
{"title":"In Memoriam: Paul M. Vanhoutte.","authors":"M. Barton, C. Cardillo","doi":"10.1113/JP279124","DOIUrl":"https://doi.org/10.1113/JP279124","url":null,"abstract":"On 23 August 2019, science lost one of its great minds: Paul Michel Georges Remi Vanhoutte, born on 26 November 1940 in Merelbeke near Ghent in Belgium, unexpectedly died in Paris after he had suffered a fall 10 days earlier. He was ‘one of the fathers of vascular biology’ (Heistad, 2008) who contributed to and shaped our understanding of how vascular endothelial cells regulate blood flow under physiological conditions and in disease.","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"183 1","pages":"5731-5737"},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83454523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mitochondrial dysfunction is a key feature of multiple diseases and thus protection of this organelle is an important therapeutic objective. The pancreatic acinar cell, which synthesises and stores digestive enzyme precursors, is the most abundant cell type in pancreatic tissue and considered to be the primary site of acute pancreatitis (AP) initiation. Early investigations at the University of Liverpool and by others discovered that precipitants of AP, including bile acids and alcohol non‐oxidative metabolites, disrupt calcium signalling in acinar cells leading to toxicity. Sustained cytosolic calcium elevations raise mitochondrial matrix calcium, triggering the opening of the mitochondrial permeability transition pore (MPTP), which results in a loss of membrane potential and ATP production vital for cellular processes (Criddle et al . 2006; Mukherjee et al . 2016) (Fig. 1). The prime consequence of pancreatic mitochondrial dysfunction in AP is necrotic cell death, the extent of which is a major determinant of clinical outcome. Subsequent studies have shown that calcium‐dependent mitochondrial dysfunction in response to AP precipitants also occurs in ductal cells, widening the cast of players implicated in the development of AP (Hegyi & Petersen, 2013). There is currently no specific therapy for the disease and protection of mitochondria by MPTP inhibition is considered a promising therapeutic approach.
{"title":"Keeping mitochondria happy – benefits of a pore choice in acute pancreatitis","authors":"D. Criddle","doi":"10.1113/JP279116","DOIUrl":"https://doi.org/10.1113/JP279116","url":null,"abstract":"Mitochondrial dysfunction is a key feature of multiple diseases and thus protection of this organelle is an important therapeutic objective. The pancreatic acinar cell, which synthesises and stores digestive enzyme precursors, is the most abundant cell type in pancreatic tissue and considered to be the primary site of acute pancreatitis (AP) initiation. Early investigations at the University of Liverpool and by others discovered that precipitants of AP, including bile acids and alcohol non‐oxidative metabolites, disrupt calcium signalling in acinar cells leading to toxicity. Sustained cytosolic calcium elevations raise mitochondrial matrix calcium, triggering the opening of the mitochondrial permeability transition pore (MPTP), which results in a loss of membrane potential and ATP production vital for cellular processes (Criddle et al . 2006; Mukherjee et al . 2016) (Fig. 1). The prime consequence of pancreatic mitochondrial dysfunction in AP is necrotic cell death, the extent of which is a major determinant of clinical outcome. Subsequent studies have shown that calcium‐dependent mitochondrial dysfunction in response to AP precipitants also occurs in ductal cells, widening the cast of players implicated in the development of AP (Hegyi & Petersen, 2013). There is currently no specific therapy for the disease and protection of mitochondria by MPTP inhibition is considered a promising therapeutic approach.","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"78 1","pages":"5741 - 5742"},"PeriodicalIF":0.0,"publicationDate":"2019-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76089829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The belief that the broad sweep of the Hodgkin–Huxley papers (Hodgkin & Huxley, 1952a,c,e,f Hodgkin et al. 1952) can be adequately summarised within a standard textbook chapter is fanciful at best and disingenuous at worst, because such summaries consist of scientific sound-bites that deprive students of the big picture; how decisive experiments create a linear narrative culminating in an internally consistent piece of work. In textbook chapters devoted to Hodgkin and Huxley’s work there are two topics that are inevitably omitted. The first is the separation of the trans-membrane current into INa and IK, the process usually described as a simple subtraction of currents recorded in Na+-free seawater from control currents, which is a gross simplification that neglects to recognise Hodgkin and Huxley’s elegant mathematical solution to the problem (Hodgkin & Huxley, 1952c). Fortunately there exists a superb account of this subject (Cronin, 1987). The second topic, and the subject of this editorial, relates to whether ion movements across a membrane conform to the independence principle. This principle, which was universally accepted at the time, derived from the equations of Teorell and Ussing, and described how the probability of the movement of ions across membranes was under the influence of electrical and chemical gradients but was independent of the presence of other ions (Teorell, 1949; Ussing, 1949). This topic appears deceptively simple upon initial inspection but consideration of the underlying mathematical foundations reveals unexpected complexity. Consider a cell bathed in saline where the influx of a particular ion can be expressed as
{"title":"Ion channels: the concept emerges","authors":"Angus M. Brown","doi":"10.1113/JP279059","DOIUrl":"https://doi.org/10.1113/JP279059","url":null,"abstract":"The belief that the broad sweep of the Hodgkin–Huxley papers (Hodgkin & Huxley, 1952a,c,e,f Hodgkin et al. 1952) can be adequately summarised within a standard textbook chapter is fanciful at best and disingenuous at worst, because such summaries consist of scientific sound-bites that deprive students of the big picture; how decisive experiments create a linear narrative culminating in an internally consistent piece of work. In textbook chapters devoted to Hodgkin and Huxley’s work there are two topics that are inevitably omitted. The first is the separation of the trans-membrane current into INa and IK, the process usually described as a simple subtraction of currents recorded in Na+-free seawater from control currents, which is a gross simplification that neglects to recognise Hodgkin and Huxley’s elegant mathematical solution to the problem (Hodgkin & Huxley, 1952c). Fortunately there exists a superb account of this subject (Cronin, 1987). The second topic, and the subject of this editorial, relates to whether ion movements across a membrane conform to the independence principle. This principle, which was universally accepted at the time, derived from the equations of Teorell and Ussing, and described how the probability of the movement of ions across membranes was under the influence of electrical and chemical gradients but was independent of the presence of other ions (Teorell, 1949; Ussing, 1949). This topic appears deceptively simple upon initial inspection but consideration of the underlying mathematical foundations reveals unexpected complexity. Consider a cell bathed in saline where the influx of a particular ion can be expressed as","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89727427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The primary means by which ion permeation through potassium channels is controlled, and the key to selective intervention in a range of pathophysiological conditions, is the process by which channels switch between non‐conducting and conducting states. Conventionally, this has been explained by a steric mechanism in which the pore alternates between two conformations: a ‘closed’ state in which the conduction pathway is occluded and an ‘open’ state in which the pathway is sufficiently wide to accommodate fully hydrated ions. Recently, however, ‘non‐canonical’ mechanisms have been proposed for some classes of K+ channels. The purpose of this review is to illuminate structural and dynamic relationships underpinning permeation control in K+ channels, indicating where additional data might resolve some of the remaining issues.
{"title":"Changing perspectives on how the permeation pathway through potassium channels is regulated","authors":"K. A. Black, Ruitao Jin, Sitong He, J. Gulbis","doi":"10.1113/JP278682","DOIUrl":"https://doi.org/10.1113/JP278682","url":null,"abstract":"The primary means by which ion permeation through potassium channels is controlled, and the key to selective intervention in a range of pathophysiological conditions, is the process by which channels switch between non‐conducting and conducting states. Conventionally, this has been explained by a steric mechanism in which the pore alternates between two conformations: a ‘closed’ state in which the conduction pathway is occluded and an ‘open’ state in which the pathway is sufficiently wide to accommodate fully hydrated ions. Recently, however, ‘non‐canonical’ mechanisms have been proposed for some classes of K+ channels. The purpose of this review is to illuminate structural and dynamic relationships underpinning permeation control in K+ channels, indicating where additional data might resolve some of the remaining issues.","PeriodicalId":22512,"journal":{"name":"The Japanese journal of physiology","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88123376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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