{"title":"The effects of G protein-coupled receptor 30 (GPR30) on cardiac glucose metabolism in diabetic ovariectomized female rats.","authors":"Mohammad Shahbazian, Faezeh Jafarynezhad, Maryam Yadeghari, Zeinab Farhadi, Sanaz Lotfi Samani, Mansour Esmailidehaj, Fatemeh Safari, Hossein Azizian","doi":"10.1515/jbcpp-2021-0374","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Diabetic cardiometabolic disorders are characterized by significant changes in cardiac metabolism and are increased in postmenopausal women, which emphasize the role of 17<i>β</i>-estradiol (E2). Despite this, there are few safe and effective pharmacological treatments for these disorders. The role of G protein-coupled estrogen receptor (GPR30), which mediates the non-genomic effects of E2, is mostly unexplored.</p><p><strong>Methods: </strong>In this study, we used ovariectomy (menopausal model) and type 2 diabetic (T2D) rats' models to evaluate the preclinical action of G-1 (GPR30 agonist) against cardiometabolic disorders. T2D was induced by a high-fat diet and a low dose of streptozotocin. G-1 was administrated for six weeks after the establishment of T2D.</p><p><strong>Results: </strong>We found that G-1 counteracts the effects of T2D and ovariectomy by increasing the body weight, reducing fasting blood sugar, heart weight, and heart weight to body weight ratio. Also, both ovariectomy and T2D led to decreases in the cardiac protein levels of hexokinase 2 (HK2) and GLUT4, while G-1-treated female rats reversed these changes and only increased HK2 protein level. In addition, T2D and ovariectomy increased glucose and glycogen content in the heart, but G-1 treatment significantly reduced them.</p><p><strong>Conclusions: </strong>In conclusion, our work demonstrates that G-1 as a selective GPR30 agonist is a viable therapeutic approach against T2D and cardiometabolic diseases in multiple preclinical female models.</p>","PeriodicalId":15352,"journal":{"name":"Journal of Basic and Clinical Physiology and Pharmacology","volume":"34 2","pages":"205-213"},"PeriodicalIF":0.0000,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"4","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Basic and Clinical Physiology and Pharmacology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1515/jbcpp-2021-0374","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Pharmacology, Toxicology and Pharmaceutics","Score":null,"Total":0}
引用次数: 4
Abstract
Background: Diabetic cardiometabolic disorders are characterized by significant changes in cardiac metabolism and are increased in postmenopausal women, which emphasize the role of 17β-estradiol (E2). Despite this, there are few safe and effective pharmacological treatments for these disorders. The role of G protein-coupled estrogen receptor (GPR30), which mediates the non-genomic effects of E2, is mostly unexplored.
Methods: In this study, we used ovariectomy (menopausal model) and type 2 diabetic (T2D) rats' models to evaluate the preclinical action of G-1 (GPR30 agonist) against cardiometabolic disorders. T2D was induced by a high-fat diet and a low dose of streptozotocin. G-1 was administrated for six weeks after the establishment of T2D.
Results: We found that G-1 counteracts the effects of T2D and ovariectomy by increasing the body weight, reducing fasting blood sugar, heart weight, and heart weight to body weight ratio. Also, both ovariectomy and T2D led to decreases in the cardiac protein levels of hexokinase 2 (HK2) and GLUT4, while G-1-treated female rats reversed these changes and only increased HK2 protein level. In addition, T2D and ovariectomy increased glucose and glycogen content in the heart, but G-1 treatment significantly reduced them.
Conclusions: In conclusion, our work demonstrates that G-1 as a selective GPR30 agonist is a viable therapeutic approach against T2D and cardiometabolic diseases in multiple preclinical female models.
期刊介绍:
The Journal of Basic and Clinical Physiology and Pharmacology (JBCPP) is a peer-reviewed bi-monthly published journal in experimental medicine. JBCPP publishes novel research in the physiological and pharmacological sciences, including brain research; cardiovascular-pulmonary interactions; exercise; thermal control; haematology; immune response; inflammation; metabolism; oxidative stress; and phytotherapy. As the borders between physiology, pharmacology and biochemistry become increasingly blurred, we also welcome papers using cutting-edge techniques in cellular and/or molecular biology to link descriptive or behavioral studies with cellular and molecular mechanisms underlying the integrative processes. Topics: Behavior and Neuroprotection, Reproduction, Genotoxicity and Cytotoxicity, Vascular Conditions, Cardiovascular Function, Cardiovascular-Pulmonary Interactions, Oxidative Stress, Metabolism, Immune Response, Hematological Profile, Inflammation, Infection, Phytotherapy.