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

Epicardial adipose tissue as target of the incretin-based therapies in cardio-metabolic pathologies: a narrative review. 心外膜脂肪组织作为以肠促胰岛素为基础的心脏代谢病理治疗的目标：叙述性回顾。

IF 1.7 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-05-01 Epub Date: 2025-03-06 DOI: 10.1139/cjpp-2024-0384

Andrea S K Pop, Maria D Dănilă, Silvia Giuchici, Darius G Buriman, Bogdan M Lolescu, Adrian Sturza, Danina M Muntean, Ana Lascu

{"title":"Epicardial adipose tissue as target of the incretin-based therapies in cardio-metabolic pathologies: a narrative review.","authors":"Andrea S K Pop, Maria D Dănilă, Silvia Giuchici, Darius G Buriman, Bogdan M Lolescu, Adrian Sturza, Danina M Muntean, Ana Lascu","doi":"10.1139/cjpp-2024-0384","DOIUrl":"10.1139/cjpp-2024-0384","url":null,"abstract":"The epicardial adipose tissue (EAT) serves in physiological conditions as a mechanical and thermal myocardial protective layer, as well as a readily available lipid-storage unit. In pathological conditions, EAT expansion becomes deleterious and is currently recognized as an independent risk factor for the progression of cardiovascular diseases. The EAT phenotypic shift from protective to pro-inflammatory/pro-oxidant is facilitated by the presence of metabolic diseases (obesity, metabolic syndrome, and diabetes), which further increase its expansion and dysregulation, favor the occurrence of complications (mainly atrial fibrillation), and promote progression towards heart failure. Glucagon-like peptide-1 (GLP-1) receptor agonists are novel antidiabetic medications belonging to the incretin class that have demonstrated efficacy beyond glycemic control, in terms of weight reduction and cardiorenal protection in patients with type 2 diabetes mellitus. The GLP-1 receptors and glucose-dependent insulinotropic polypeptide (GIP) receptors are expressed in the human EAT and are targeted by an increasing number of pharmacological agonists, with pleiotropic protective effects on EAT structure and function. Herein we review the literature characterizing the benefits of GLP-1 and GIP receptors activation by single and dual agonists with particular emphasis on their effects on EAT and highlight the role of incretin-based therapy for the management of cardiometabolic pathologies.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"182-192"},"PeriodicalIF":1.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572263","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

White matter microglia morphological changes with aging in guinea pig offspring born growth restricted. 出生时生长受限的豚鼠后代白质小胶质细胞形态随年龄变化。

IF 1.7 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-05-01 Epub Date: 2025-04-22 DOI: 10.1139/cjpp-2024-0275

Timothy B Nunes, Karen L Nygard, Marc C J Courchesne, Shawn N Whitehead, Bryan S Richardson, Timothy R H Regnault

{"title":"White matter microglia morphological changes with aging in guinea pig offspring born growth restricted.","authors":"Timothy B Nunes, Karen L Nygard, Marc C J Courchesne, Shawn N Whitehead, Bryan S Richardson, Timothy R H Regnault","doi":"10.1139/cjpp-2024-0275","DOIUrl":"10.1139/cjpp-2024-0275","url":null,"abstract":"Fetal growth restriction is implicated in the programming of later-life neurodegeneration. We hypothesized that growth-restricted offspring would show accelerated changes to microglial white matter morphology, relative to controls. Control guinea pig sows were fed ad libitum, while maternal nutrient restriction sows received 70% of control diet switched to 90% from mid-gestation. Offspring were sacrificed at ∼26 days (neonate) or ∼110 days (adult) postpartum. Coronal brain sections from the frontal cortex were subject to IBA1 staining for microglial detection and analyzed by machine learning software. At birth, total body weight of growth-restricted offspring was reduced relative to control (p < 0.0001) with postnatal catch-up growth observed. Microglial density was reduced in the corpus callosum of control (p < 0.05) and growth-restricted (p = 0.13) adults, relative to neonates. Adults from both groups showed greater IBA1-positive area in the cingulum and periventricular white matter (p < 0.05) and increased microglial fractal dimension in the corpus callosum (p < 0.10) and periventricular white matter (p < 0.05), relative to neonates. At the time points studied, we report age-related changes in white matter microglial morphology. However, maternal nutrient restriction leading to fetal growth restriction in guinea pigs does not appear to exacerbate these white matter microglia morphological changes as a marker for later-life neurodegeneration.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"193-199"},"PeriodicalIF":1.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985145","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

Causality assessment of adverse events by healthcare professionals in an academic hospital setting: a descriptive retrospective study. 学术医院医疗专业人员不良事件的因果关系评估：一项描述性回顾性研究。

IF 1.7 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-05-01 Epub Date: 2025-02-21 DOI: 10.1139/cjpp-2024-0268

Sonia Corbin, Maude Lavallée, Pallavi Pradhan, Magalie Thibault, Julie Méthot, Laura Blonde Guefack Djiokeng, Anick Bérard, Marie-Eve Piché, Fernanda Raphael Escobar Gimenes, Rosalie Darveau, Isabelle Cloutier, Jacinthe Leclerc

引用次数: 0

The calcium-sensitive receptor in the pathogenesis of sepsis. 钙敏感受体在败血症发病机制中的作用。

IF 1.7 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2025-04-30 DOI: 10.1139/cjpp-2025-0004

Bin Yu, Xuelian Li, Li Yang, Cheng Han, Jun Tan, Xiaoyan Yu, Min Li, Zhe Xu, Xiongying Chen

{"title":"The calcium-sensitive receptor in the pathogenesis of sepsis.","authors":"Bin Yu, Xuelian Li, Li Yang, Cheng Han, Jun Tan, Xiaoyan Yu, Min Li, Zhe Xu, Xiongying Chen","doi":"10.1139/cjpp-2025-0004","DOIUrl":"10.1139/cjpp-2025-0004","url":null,"abstract":"Sepsis is an organ dysfunction caused by the body's dysfunctional response to infection, which is one of the most important causes of death in critically ill patients. It is characterized by high morbidity, high mortality, and high treatment costs. Currently, the treatment of sepsis relies mainly on supportive therapy, and there is a lack of targeted intervention ways. Studying the pathogenesis of sepsis and exploring new therapeutic targets are of great theoretical and clinical importance. Calcium-sensitive receptor (CaSR) is a cell membrane receptor belonging to the family of G protein-coupled receptors and is widely distributed in various tissues and organs. Research indicates that CaSR plays a role in mitigating sepsis-induced organ dysfunction, exhibiting tissue-specific protective effects in certain tissues while inducing inflammatory responses in others. Elucidating these dual effects and the underlying signaling pathways could facilitate the development of targeted therapies for sepsis-related organ damage. This review summarizes recent literature and evidence on CaSR signaling in sepsis-induced organ dysfunction. In addition, we provide an up-to-date schematic of the most important and likely molecular signaling pathways associated with CaSR in sepsis.","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":"143964292","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

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

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

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