Early cardiac changes in a rat model of prediabetes: brain natriuretic peptide overexpression seems to be the best marker
Autor(a) principal: | |
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Data de Publicação: | 2013 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/109722 https://doi.org/10.1186/1475-2840-12-44 |
Resumo: | Background: Diabetic cardiomyopathy (DCM) is defined as structural and functional changes in the myocardium due to metabolic and cellular abnormalities induced by diabetes mellitus (DM). The impact of prediabetic conditions on the cardiac tissue remains to be elucidated. The goal of this study was to elucidate whether cardiac dysfunction is already present in a state of prediabetes, in the presence of insulin resistance, and to unravel the underlying mechanisms, in a rat model without obesity and hypertension as confounding factors. Methods: Two groups of 16-week-old Wistar rats were tested during a 9 week protocol: high sucrose (HSu) diet group (n = 7) – rats receiving 35% of sucrose in drinking water vs the vehicle control group (n = 7). The animal model was characterized in terms of body weight (BW) and the glycemic, insulinemic and lipidic profiles. The following parameters were assessed to evaluate possible early cardiac alterations and underlying mechanisms: blood pressure, heart rate, heart and left ventricle (LV) trophism indexes, as well as the serum and tissue protein and/or the mRNA expression of markers for fibrosis, hypertrophy, proliferation, apoptosis, angiogenesis, endothelial function, inflammation and oxidative stress. Results: The HSu-treated rats presented normal fasting plasma glucose (FPG) but impaired glucose tolerance (IGT), accompanied by hyperinsulinemia and insulin resistance (P < 0.01), confirming this rat model as prediabetic. Furthermore, although hypertriglyceridemia (P < 0.05) was observed, obesity and hypertension were absent. Regarding the impact of the HSu diet on the cardiac tissue, our results indicated that 9 weeks of treatment might be associated with initial cardiac changes, as suggested by the increased LV weight/BW ratio (P < 0.01) and a remarkable brain natriuretic peptide (BNP) mRNA overexpression (P < 0.01), together with a marked trend for an upregulation of other important mediators of fibrosis, hypertrophy, angiogenesis and endothelial lesions, as well as oxidative stress. The inflammatory and apoptotic markers measured were unchanged. Conclusions: This animal model of prediabetes/insulin resistance could be an important tool to evaluate the early cardiac impact of dysmetabolism (hyperinsulinemia and impaired glucose tolerance with fasting normoglycemia), without confounding factors such as obesity and hypertension. Left ventricle hypertrophy is already present and brain natriuretic peptide seems to be the best early marker for this condition. |
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Early cardiac changes in a rat model of prediabetes: brain natriuretic peptide overexpression seems to be the best markerBrain natriuretic peptideDiabetic cardiomyopathyFibrosisHypertrophyHigh-sucrose dietPrediabetesAnimalsBiomarkersBlood GlucoseEarly DiagnosisGene Expression RegulationHypertrophy, Left VentricularInsulin ResistanceMaleNatriuretic Peptide, BrainPrediabetic StateRatsRats, WistarDisease Models, AnimalBackground: Diabetic cardiomyopathy (DCM) is defined as structural and functional changes in the myocardium due to metabolic and cellular abnormalities induced by diabetes mellitus (DM). The impact of prediabetic conditions on the cardiac tissue remains to be elucidated. The goal of this study was to elucidate whether cardiac dysfunction is already present in a state of prediabetes, in the presence of insulin resistance, and to unravel the underlying mechanisms, in a rat model without obesity and hypertension as confounding factors. Methods: Two groups of 16-week-old Wistar rats were tested during a 9 week protocol: high sucrose (HSu) diet group (n = 7) – rats receiving 35% of sucrose in drinking water vs the vehicle control group (n = 7). The animal model was characterized in terms of body weight (BW) and the glycemic, insulinemic and lipidic profiles. The following parameters were assessed to evaluate possible early cardiac alterations and underlying mechanisms: blood pressure, heart rate, heart and left ventricle (LV) trophism indexes, as well as the serum and tissue protein and/or the mRNA expression of markers for fibrosis, hypertrophy, proliferation, apoptosis, angiogenesis, endothelial function, inflammation and oxidative stress. Results: The HSu-treated rats presented normal fasting plasma glucose (FPG) but impaired glucose tolerance (IGT), accompanied by hyperinsulinemia and insulin resistance (P < 0.01), confirming this rat model as prediabetic. Furthermore, although hypertriglyceridemia (P < 0.05) was observed, obesity and hypertension were absent. Regarding the impact of the HSu diet on the cardiac tissue, our results indicated that 9 weeks of treatment might be associated with initial cardiac changes, as suggested by the increased LV weight/BW ratio (P < 0.01) and a remarkable brain natriuretic peptide (BNP) mRNA overexpression (P < 0.01), together with a marked trend for an upregulation of other important mediators of fibrosis, hypertrophy, angiogenesis and endothelial lesions, as well as oxidative stress. The inflammatory and apoptotic markers measured were unchanged. Conclusions: This animal model of prediabetes/insulin resistance could be an important tool to evaluate the early cardiac impact of dysmetabolism (hyperinsulinemia and impaired glucose tolerance with fasting normoglycemia), without confounding factors such as obesity and hypertension. Left ventricle hypertrophy is already present and brain natriuretic peptide seems to be the best early marker for this condition.Springer Nature2013-03-07info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/109722http://hdl.handle.net/10316/109722https://doi.org/10.1186/1475-2840-12-44eng1475-2840Nunes, SaraSoares, EdnaFernandes, JoãoViana, Sofia D.Carvalho, EugeniaPereira, Frederico C.Reis, Flávioinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-10-24T10:28:51Zoai:estudogeral.uc.pt:10316/109722Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:25:52.549989Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Early cardiac changes in a rat model of prediabetes: brain natriuretic peptide overexpression seems to be the best marker |
title |
Early cardiac changes in a rat model of prediabetes: brain natriuretic peptide overexpression seems to be the best marker |
spellingShingle |
Early cardiac changes in a rat model of prediabetes: brain natriuretic peptide overexpression seems to be the best marker Nunes, Sara Brain natriuretic peptide Diabetic cardiomyopathy Fibrosis Hypertrophy High-sucrose diet Prediabetes Animals Biomarkers Blood Glucose Early Diagnosis Gene Expression Regulation Hypertrophy, Left Ventricular Insulin Resistance Male Natriuretic Peptide, Brain Prediabetic State Rats Rats, Wistar Disease Models, Animal |
title_short |
Early cardiac changes in a rat model of prediabetes: brain natriuretic peptide overexpression seems to be the best marker |
title_full |
Early cardiac changes in a rat model of prediabetes: brain natriuretic peptide overexpression seems to be the best marker |
title_fullStr |
Early cardiac changes in a rat model of prediabetes: brain natriuretic peptide overexpression seems to be the best marker |
title_full_unstemmed |
Early cardiac changes in a rat model of prediabetes: brain natriuretic peptide overexpression seems to be the best marker |
title_sort |
Early cardiac changes in a rat model of prediabetes: brain natriuretic peptide overexpression seems to be the best marker |
author |
Nunes, Sara |
author_facet |
Nunes, Sara Soares, Edna Fernandes, João Viana, Sofia D. Carvalho, Eugenia Pereira, Frederico C. Reis, Flávio |
author_role |
author |
author2 |
Soares, Edna Fernandes, João Viana, Sofia D. Carvalho, Eugenia Pereira, Frederico C. Reis, Flávio |
author2_role |
author author author author author author |
dc.contributor.author.fl_str_mv |
Nunes, Sara Soares, Edna Fernandes, João Viana, Sofia D. Carvalho, Eugenia Pereira, Frederico C. Reis, Flávio |
dc.subject.por.fl_str_mv |
Brain natriuretic peptide Diabetic cardiomyopathy Fibrosis Hypertrophy High-sucrose diet Prediabetes Animals Biomarkers Blood Glucose Early Diagnosis Gene Expression Regulation Hypertrophy, Left Ventricular Insulin Resistance Male Natriuretic Peptide, Brain Prediabetic State Rats Rats, Wistar Disease Models, Animal |
topic |
Brain natriuretic peptide Diabetic cardiomyopathy Fibrosis Hypertrophy High-sucrose diet Prediabetes Animals Biomarkers Blood Glucose Early Diagnosis Gene Expression Regulation Hypertrophy, Left Ventricular Insulin Resistance Male Natriuretic Peptide, Brain Prediabetic State Rats Rats, Wistar Disease Models, Animal |
description |
Background: Diabetic cardiomyopathy (DCM) is defined as structural and functional changes in the myocardium due to metabolic and cellular abnormalities induced by diabetes mellitus (DM). The impact of prediabetic conditions on the cardiac tissue remains to be elucidated. The goal of this study was to elucidate whether cardiac dysfunction is already present in a state of prediabetes, in the presence of insulin resistance, and to unravel the underlying mechanisms, in a rat model without obesity and hypertension as confounding factors. Methods: Two groups of 16-week-old Wistar rats were tested during a 9 week protocol: high sucrose (HSu) diet group (n = 7) – rats receiving 35% of sucrose in drinking water vs the vehicle control group (n = 7). The animal model was characterized in terms of body weight (BW) and the glycemic, insulinemic and lipidic profiles. The following parameters were assessed to evaluate possible early cardiac alterations and underlying mechanisms: blood pressure, heart rate, heart and left ventricle (LV) trophism indexes, as well as the serum and tissue protein and/or the mRNA expression of markers for fibrosis, hypertrophy, proliferation, apoptosis, angiogenesis, endothelial function, inflammation and oxidative stress. Results: The HSu-treated rats presented normal fasting plasma glucose (FPG) but impaired glucose tolerance (IGT), accompanied by hyperinsulinemia and insulin resistance (P < 0.01), confirming this rat model as prediabetic. Furthermore, although hypertriglyceridemia (P < 0.05) was observed, obesity and hypertension were absent. Regarding the impact of the HSu diet on the cardiac tissue, our results indicated that 9 weeks of treatment might be associated with initial cardiac changes, as suggested by the increased LV weight/BW ratio (P < 0.01) and a remarkable brain natriuretic peptide (BNP) mRNA overexpression (P < 0.01), together with a marked trend for an upregulation of other important mediators of fibrosis, hypertrophy, angiogenesis and endothelial lesions, as well as oxidative stress. The inflammatory and apoptotic markers measured were unchanged. Conclusions: This animal model of prediabetes/insulin resistance could be an important tool to evaluate the early cardiac impact of dysmetabolism (hyperinsulinemia and impaired glucose tolerance with fasting normoglycemia), without confounding factors such as obesity and hypertension. Left ventricle hypertrophy is already present and brain natriuretic peptide seems to be the best early marker for this condition. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013-03-07 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/109722 http://hdl.handle.net/10316/109722 https://doi.org/10.1186/1475-2840-12-44 |
url |
http://hdl.handle.net/10316/109722 https://doi.org/10.1186/1475-2840-12-44 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1475-2840 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Springer Nature |
publisher.none.fl_str_mv |
Springer Nature |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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