Canadian journal of physiology and pharmacology最新文献_第2页

Disproportionality Analysis of ALK Inhibitor-Induced Hemolytic Adverse Events: A Pharmacovigilance Study Using the FDA Adverse Event Reporting System Database. ALK抑制剂诱导的溶血不良事件的歧化分析：使用FDA不良事件报告系统数据库的药物警戒研究。

IF 1.7 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-04-30 DOI: 10.1139/cjpp-2025-0065

Connor Frey

{"title":"Disproportionality Analysis of ALK Inhibitor-Induced Hemolytic Adverse Events: A Pharmacovigilance Study Using the FDA Adverse Event Reporting System Database.","authors":"Connor Frey","doi":"10.1139/cjpp-2025-0065","DOIUrl":"https://doi.org/10.1139/cjpp-2025-0065","url":null,"abstract":"Objective: ALK inhibitors have transformed treatment for ALK-rearranged malignancies, particularly NSCLC, by disrupting oncogenic signalling. However, hematologic adverse effects, including hemolysis, have emerged as concerns, especially with alectinib. This study evaluates the prevalence of hemolytic events associated with ALK inhibitors using FDA Adverse Event Reporting System (FAERS) data.Methods: A retrospective pharmacovigilance analysis was conducted using FAERS data (2013-2023). Disproportionality analysis with OpenVigil 2.1 assessed associations between ALK inhibitors and hemolysis-related events. Reporting odds ratios (RORs) were calculated, with statistical significance defined as ROR >2.00 and a lower 95% confidence interval (CI) bound >1.00.Results: Alectinib exhibited strong associations with hemolysis (ROR 24.01, 95% CI: 17.88-32.24; 45 reports) and bilirubin increase (ROR 18.86, 95% CI: 15.92-22.34; 138 reports). Crizotinib and ceritinib showed weaker signals, while brigatinib and lorlatinib had no significant associations.Discussion: The findings highlight alectinibs potential hemolytic risk, necessitating hematologic monitoring. Proposed mechanisms include immune-mediated hemolysis, direct cytotoxicity, and metabolic variability. Routine hemoglobin and bilirubin assessments, along with clinical vigilance, are essential. Further studies are needed to elucidate mechanisms of causality and optimize patient safety.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Maternal high-fat diet promotes enhanced airway hyperresponsiveness and impaired bronchodilation response in adult male offspring. 母体高脂肪饮食促进成年雄性后代气道高反应性增强和支气管扩张反应受损。

IF 1.7 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-04-30 DOI: 10.1139/cjpp-2024-0397

Luiz Otávio Lourenço, Évila da Silva Lopes Salles, Ricardo Murilo Pereira Emídio, Valdemar Antonio Paffaro Junior, Roseli Soncini, Bruno Zavan

{"title":"Maternal high-fat diet promotes enhanced airway hyperresponsiveness and impaired bronchodilation response in adult male offspring.","authors":"Luiz Otávio Lourenço, Évila da Silva Lopes Salles, Ricardo Murilo Pereira Emídio, Valdemar Antonio Paffaro Junior, Roseli Soncini, Bruno Zavan","doi":"10.1139/cjpp-2024-0397","DOIUrl":"10.1139/cjpp-2024-0397","url":null,"abstract":"Obesity induced by a high-fat diet (HFD) is a growing global health concern, often linked to numerous metabolic and respiratory disorders. This study investigates the impact of a maternal HFD on the respiratory physiology of adult offspring, emphasizing the potential for fetal programming to exacerbate airway responsiveness. Adult male offspring from dams fed a HFD or a control diet during gestation were submitted to ventilatory mechanical analysis following bronchoconstrictor and bronchodilator challenge. Offspring from the HFD group demonstrated increased body weight, elevated blood glucose levels, heightened airway responsiveness to methacholine-induced bronchoconstriction, and impaired bronchodilator efficacy compared to controls. These findings underscore the potential long-term impact of maternal nutrition on offspring respiratory health. The study also highlights the necessity of identifying critical therapeutic targets for managing respiratory dysfunction in populations exposed to maternal obesity, intending to improve treatment outcomes and prevent related respiratory complications.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Naringin prevents the impairment of hepatic mitochondrial function in diabetic rats. 柚皮苷对糖尿病大鼠肝线粒体功能损害的预防作用。

IF 1.7 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-04-25 DOI: 10.1139/cjpp-2024-0357

María A Rizzi, Adriana Pérez, Solange Guizzardi, Nori Tolosa de Talamoni, Valeria A Rodríguez

{"title":"Naringin prevents the impairment of hepatic mitochondrial function in diabetic rats.","authors":"María A Rizzi, Adriana Pérez, Solange Guizzardi, Nori Tolosa de Talamoni, Valeria A Rodríguez","doi":"10.1139/cjpp-2024-0357","DOIUrl":"https://doi.org/10.1139/cjpp-2024-0357","url":null,"abstract":"We previously demonstrated that naringin (NAR) protects against liver damage in streptozotocin (STZ)-induced diabetes in rats. The aim of this study was to elucidate whether NAR is also able to protect the functioning, biogenesis and dynamics of the liver mitochondria in diabetic rats (DM). The activities of isocitrate dehydrogenase and malate dehydrogenase from the Krebs cycle, complex I-III from electron chain and adenosine triphosphate synthase were decreased in DM rats, effects that were blocked by NAR. The gene expression of mitofusin-2 and GTPase dynamin-related protein 1, markers of mitochondrial fusion and fission, were decreased in DM rats, which was prevented by NAR. Total glutathione was decreased and protein carbonyl contents as well as the activity of the antioxidant enzymes were increased in DM rats. All these changes were blocked by NAR. In conclusion, NAR protects the liver mitochondria from DM rats avoiding changes in the activity of Krebs cycle, the respiratory chain and the oxidative phosphorylation as well as preventing alterations in the fusion-fission processes. These effects are mediated, at least in part, by decreasing oxidative stress and anomalies in the enzymatic antioxidant system. Further studies are necessary to validate efficacy and safety of NAR for human use.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring the supraspinal antihyperalgesic effects of levetiracetam in the rat model of chronic constriction injury. 探讨左乙拉西坦对大鼠慢性缩窄性损伤的脊髓上抗痛觉作用。

IF 1.7 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-04-17 DOI: 10.1139/cjpp-2024-0302

Feyza Alyu Altinok, Michele Petrella, Alessio Masi, Anna Maria Borruto, Roberto Ciccocioppo, Yusuf Ozturk

{"title":"Exploring the supraspinal antihyperalgesic effects of levetiracetam in the rat model of chronic constriction injury.","authors":"Feyza Alyu Altinok, Michele Petrella, Alessio Masi, Anna Maria Borruto, Roberto Ciccocioppo, Yusuf Ozturk","doi":"10.1139/cjpp-2024-0302","DOIUrl":"https://doi.org/10.1139/cjpp-2024-0302","url":null,"abstract":"Neuropathic pain severely impacts quality of life and effective treatments are needed. To address this, the present study investigated the antihyperalgesic mechanisms of levetiracetam administered at the supraspinal level, together with its effects on ion channel activities. The ventral posterolateral nucleus of the thalamus was selected as the location for micro-injection. Thermal hyperalgesia and mechanical allodynia were assessed via in vivo experiments using the Hargreave's and e-Von Frey apparatus, respectively. Levetiracetam displayed statistically meaningful time and dose-dependent effects in the chronic constriction injury model, with statistical probability values less than 0.05. It was discovered that the antihyperalgesic effects were more pronounced in mechanical allodynia. Electrophysiological studies conducted through whole-cell patch clamp recordings indicated that levetiracetam tended to activate or increase the permeability of one or more channels for ion flow that are active only at hyperpolarized membrane potentials (-130 to -90 mV), suggesting the potential participation of hyperpolarization-activated cyclic nucleotide-gated, inwardly-rectifying K+, or G protein-gated inwardly-rectifying K+ channels. The findings could guide future drug development studies towards levetiracetam and its derivatives as effective treatments for neuropathic pain.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nampt: a new therapeutic target for modulating NAD⁺ levels in metabolic, cardiovascular, and neurodegenerative diseases. Nampt：在代谢、心血管和神经退行性疾病中调节NAD+水平的新治疗靶点

IF 1.7 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-04-09 DOI: 10.1139/cjpp-2024-0400

Ravikumar Manickam, Sandhya Santhana, Wanling Xuan, Kirpal S Bisht, Srinivas M Tipparaju

{"title":"Nampt: a new therapeutic target for modulating NAD+ levels in metabolic, cardiovascular, and neurodegenerative diseases.","authors":"Ravikumar Manickam, Sandhya Santhana, Wanling Xuan, Kirpal S Bisht, Srinivas M Tipparaju","doi":"10.1139/cjpp-2024-0400","DOIUrl":"10.1139/cjpp-2024-0400","url":null,"abstract":"NAD+ is an important cofactor involved in regulating many biochemical processes in cells. An imbalance in NAD+/NADH ratio is linked to many diseases. NAD+ is depleted in diabetes, cardiovascular and neurodegenerative diseases, and in aging, and is increased in tumor cells. NAD+ is generated in cells via the de novo, Preiss-Handler, and salvage pathways. Most of the cellular NAD+ is generated through Nampt activation, a key rate-limiting enzyme that is involved in the salvage pathway. Restoration of NAD+/NADH balance offers therapeutic advantages for improving tissue homeostasis and function. NAD+ is known to benefit and restore the body's physiological mechanisms, including DNA replication, chromatin and epigenetic modifications, and gene expression. Recent studies elucidate the role of NAD+ in cells utilizing transgenic mouse models. Translational new therapeutics are positioned to utilize the NAD+ restoration strategies for overcoming the drawbacks that exist in the pharmacological toolkit. The present review highlights the significance of Nampt-NAD+ axis as a major player in energy metabolism and provides an overview with insights into future strategies, providing pharmacological advantages to address current and future medical needs.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects of acute aerobic exercise on skeletal muscle and liver glucose metabolism in male rodents with type 1 diabetes. 急性有氧运动对1型糖尿病雄性啮齿动物骨骼肌和肝脏葡萄糖代谢的影响

IF 1.7 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-04-01 Epub Date: 2025-01-15 DOI: 10.1139/cjpp-2024-0226

Justin A Camenzuli, Mitchell J Sammut, Theres Tijo, C W James Melling

{"title":"Effects of acute aerobic exercise on skeletal muscle and liver glucose metabolism in male rodents with type 1 diabetes.","authors":"Justin A Camenzuli, Mitchell J Sammut, Theres Tijo, C W James Melling","doi":"10.1139/cjpp-2024-0226","DOIUrl":"10.1139/cjpp-2024-0226","url":null,"abstract":"Aerobic exercise (AE) is associated with a significant hypoglycemia risk in individuals with type 1 diabetes mellitus (T1DM). However, the mechanisms in the liver and skeletal muscle governing exercise-induced hypoglycemia in T1DM are poorly understood. This study examined the effects of a 60-min bout of AE on hepatic and muscle glucose metabolism in T1DM rats. Nineteen male Sprague-Dawley rats were divided into sedentary (SC; n = 5) and T1DM (DSC; n = 14) groups. T1DM rats were subcategorized into pre-exercise (DPRE; n = 6) and post-exercise (DPOST; n = 8). DPOST were sacrificed immediately after 60 min of AE. Results demonstrate that DPOST animals experienced reductions in BG following 30 and 60 min of AE compared to pre-exercise. Both DPRE and DPOST animals exhibited lower hepatic glycogen content, while muscle glycogen did not differ, suggesting impaired glycogenolysis in T1DM. Hepatic glucose-6-phosphatase content, and muscle and hepatic protein kinase B phosphorylation were significantly greater in DPOST animals, suggesting elevated gluconeogenesis and insulin stimulation during exercise. Glycogen phosphorylase activity did not differ between groups. These data suggest that drops in BG during AE in T1DM were due to lower glycogen levels in the liver and muscle and a lack of muscle glycogen utilization; leading to a reliance on gluconeogenesis and BG.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"123-133"},"PeriodicalIF":1.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Histamine H₃ receptor activation increases the firing of striatal medium spiny neurons in slices from infantile rats. 组胺H3受体的激活增加了幼鼠纹状体中棘神经元的放电。

IF 1.7 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-04-01 Epub Date: 2025-02-13 DOI: 10.1139/cjpp-2024-0240

Carolina González-Sandoval, Isabel Godínez-Ramos, José-Antonio Arias-Montaño, Jaime Barral

{"title":"Histamine H3 receptor activation increases the firing of striatal medium spiny neurons in slices from infantile rats.","authors":"Carolina González-Sandoval, Isabel Godínez-Ramos, José-Antonio Arias-Montaño, Jaime Barral","doi":"10.1139/cjpp-2024-0240","DOIUrl":"10.1139/cjpp-2024-0240","url":null,"abstract":"Striatal medium spiny neurons (MSN) form two subpopulations (MSN-D1 and MSN-D2) according to the expression of dopamine D1 or D2 receptors and their target regions. The activation of postsynaptic histamine H1 and H2 receptors increases MSN-D1 and MSN-D2 excitability. Since MSN also express H3 receptors (H3Rs), in this work we explored the effect of their activation on MSN firing. Electrophysiological recordings (whole-cell patch-clamp, current-clamp mode) were conducted on forebrain slices from infantile rats (12-16 postnatal days). In both MSN-D1 and MSN-D2 perfusion with the H3R agonist immepip (1 µmol/L) increased neuronal firing evoked by current injection, an effect reproduced by R-α-methylhistamine (1 µmol/L) and prevented by the antagonist clobenpropit (10 µmol/L). Blockade of N- or P/Q-type voltage-activated calcium channels by ω-conotoxin-GVIA (1 µmol/L) or ω-agatoxin-TK (400 nmol/L) increased MSN firing but did not preclude the immepip effect. The potassium channel blockers 4-aminopyridine (1 mmol/L) and tetraethylammonium (300 µmol/L) increased neuronal firing and prevented the immepip action. Likewise, the KV7 channel blocker XE-991 (10 µmol/L) and the muscarinic receptor agonist carbachol (10 µmol/L) increased MSN firing frequency and occluded the immepip effect. These data indicate that the activation of postsynaptic H3Rs facilitates MSN-D1 and MSN-D2 firing by inhibiting KV7 potassium channels.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"134-145"},"PeriodicalIF":1.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The addictive process of opioids: current and novel interventions in opioid use disorder. 阿片类药物的成瘾过程：阿片类药物使用障碍的当前和新的干预措施。

IF 1.7 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-04-01 Epub Date: 2025-02-11 DOI: 10.1139/cjpp-2024-0281

James M Duerksen, Matthew Ramjiawan, Julia Witt, Shirley Fitzpatrick-Wong, Paramjit S Tappia, Bram Ramjiawan, Behzad Mansouri, Jitender Sareen, Erin Knight

{"title":"The addictive process of opioids: current and novel interventions in opioid use disorder.","authors":"James M Duerksen, Matthew Ramjiawan, Julia Witt, Shirley Fitzpatrick-Wong, Paramjit S Tappia, Bram Ramjiawan, Behzad Mansouri, Jitender Sareen, Erin Knight","doi":"10.1139/cjpp-2024-0281","DOIUrl":"10.1139/cjpp-2024-0281","url":null,"abstract":"The growing epidemic of opioid misuse presents numerous challenges for healthcare practitioners and patients alike as friction exists between ease of use and efficacy, and potential for overuse and addiction. With over 82 000 deaths related to opioid overdose in North America in 2020, it is imperative to gain a better understanding of the underlying mechanisms behind the addiction process, as well as the current methods being used in the arsenal against this disease. The current best pharmacological approaches for mediating opioid use disorder are methadone, buprenorphine, naltrexone, and naloxone, which act on opioid receptors to produce diverse effects based upon the patients' needs. The variety of effects that these drugs produce, which include removing opioid withdrawal, reversing overdose effects, and blocking opioid properties, makes this arsenal of therapeutics a global necessity in addressing the opioid use epidemic. Accordingly, this narrative review provides a summary of the available data regarding the physiological processes by which opioid addiction takes place and discusses the current and future potential of interventional methods used to mitigate opioid use disorder. The mechanisms of action and subsequent functional outcomes must be understood to reduce the number of opioid-related deaths worldwide.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"111-122"},"PeriodicalIF":1.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Polygenic scores of obesity in childhood based on summary statistics from adults versus children. 儿童肥胖的多基因评分基于成人与儿童的汇总统计。

IF 1.7 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-03-25 DOI: 10.1139/cjpp-2024-0221

Danick Goulet, Michel Boivin, Christopher Gravel, Julian Little, Isabelle Ouellet-Morin, Jean-Philippe Gouin, Lise Dubois

{"title":"Polygenic scores of obesity in childhood based on summary statistics from adults versus children.","authors":"Danick Goulet, Michel Boivin, Christopher Gravel, Julian Little, Isabelle Ouellet-Morin, Jean-Philippe Gouin, Lise Dubois","doi":"10.1139/cjpp-2024-0221","DOIUrl":"10.1139/cjpp-2024-0221","url":null,"abstract":"The lack of polygenic scores (PGSs) developed for body mass index (BMI) in children may be problematic because the genetic architecture characterizing BMI changes throughout life. This study aims to describe the genetic susceptibility to obesity in children and to compare two PGSs based on data from adults and children and their association with BMI and discrimination of obesity. The study sample comprises 717 participants aged 4-13 years. Adult- and child-based PGSs were evaluated by examining (1) mean BMI across polygenic score risk categories, (2) the capacity to identify obesity with logistic regression, and (3) the linear association with BMI z-scores using linear regression. Increases in one standardized unit of adult-based PGS were related to a stronger increase in BMI z-score (β = 0.24-0.39) than PGS derived in children (β = 0.21-0.30). The association between obesity and the child score was higher (OR = 1.75-2.33) than that for the adult score (OR = 1.74-2.06) for the age group 4-7 years. The inverse was observed for the age group 8-13 years (ORchild 1.56-1.79 vs. ORadult 1.78-2.54). Both adult- and child-based PGSs show strong associations with BMI and risk of obesity, with the adult-based score standing out from 8 years old.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Right ventricular dysfunction in preclinical models of type I and type II diabetes. 1型和2型糖尿病临床前模型右心室功能障碍

IF 1.7 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-03-01 Epub Date: 2024-12-18 DOI: 10.1139/cjpp-2024-0195

Sydney M Polson, Joshua P Thornburg, Benjamin D McNair, Christian Z Cook, Elizabeth A Straight, Kevin C Fontana, Caleb R Hoopes, Sreejayan Nair, Danielle R Bruns

{"title":"Right ventricular dysfunction in preclinical models of type I and type II diabetes.","authors":"Sydney M Polson, Joshua P Thornburg, Benjamin D McNair, Christian Z Cook, Elizabeth A Straight, Kevin C Fontana, Caleb R Hoopes, Sreejayan Nair, Danielle R Bruns","doi":"10.1139/cjpp-2024-0195","DOIUrl":"10.1139/cjpp-2024-0195","url":null,"abstract":"Diabetic cardiomyopathy (DCM) is a growing clinical entity and major health burden characterized by comorbid diabetes mellitus and heart failure. DCM has been commonly associated with impaired function of the left ventricle (LV); however, DCM likely also occurs in the right ventricle (RV) which has distinct physiology and pathophysiology from the LV. RV dysfunction is the strongest determinant of mortality in several clinical contexts yet remains poorly studied in diabetes. We investigated RV-specific pathophysiology using two models of diabetes-a well-characterized type 2 diabetes (T2DM) model of high-fat diet and low-dose streptozotocin (STZ) in the mouse and a large animal model of type I diabetes in domestic pigs rendered diabetic with STZ. RV global and systolic function deteriorated with diabetes, alongside hypertrophic and fibrotic remodeling. We report evidence of impaired RV insulin sensitivity, dysregulated RV metabolic gene expression, and impaired mitochondrial dynamics. Importantly, while some of these outcomes were similar to those widely reported in the LV, others were not, such as unchanged antioxidant gene expression and regulators of fatty acid uptake. Importantly, these RV-specific changes occurred in both male and female T2DM mice, together emphasizing the importance of distinguishing the RV from the LV when studying DCM and begging the consideration of RV-specific therapies.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"86-97"},"PeriodicalIF":1.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0