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1.
J Diabetes Complications ; 35(6): 107913, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33867245

RESUMO

AIMS: Prevalence and risk factors of pre-symptomatic left ventricular systolic dysfunction (LVSD) in individuals with type 1 diabetes (T1D) have not been adequately studied. The present cross-sectional study assessed the prevalence of early LVSD in asymptomatic patients with type 1 diabetes and investigated potential risk factors. METHODS: Consecutive patients with T1D, free of cardiovascular disease and significant evident microvascular complications were examined. LVSD was assessed by speckle-tracking echocardiography and calculation of global longitudinal strain (GLS). Abnormal GLS was defined as a value>-18.7%. We looked for possible associations between the presence of LVSD and patient demographic, clinical and laboratory characteristics, as well as with autonomic nervous system (ANS) function and arterial stiffness. RESULTS: We enrolled 155 T1D patients (29.7% men, age 36.7 ±â€¯13.1 years, diabetes duration 19.1 ±â€¯10.0 years, HbA1c 7.5 ±â€¯1.4% [58 ±â€¯15 mmol/mol]). Early LVSD was prevalent in 53 (34.2%) patients. Multivariable analysis identified male gender (OR:4.14; 95% CI:1.39-12.31, p = 0.011), HbA1c (OR:1.59 per 1% increase; 95% CI:1.11-2.28, p = 0.011), glomerular filtration rate (GFR, OR:0.97; 95% CI:0.95-0.99, p = 0.010) and BMI (OR:1.19; 95% CI:1.06-1.34, p = 0.003) as independent predictors of LVSD presence. CONCLUSIONS: Early subclinical LVSD is a common finding in asymptomatic patients with T1D, free of macrovascular and significant microvascular complications. Apart from chronic hyperglycemia, increased adiposity may be implicated in its etiology. Further investigation is warranted to identify patients at high risk for whom early screening is required and to determine possible associations between risk markers identified in the present analysis and long-term outcomes.


Assuntos
Diabetes Mellitus Tipo 1 , Disfunção Ventricular Esquerda , Adulto , Estudos Transversais , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Feminino , Hemoglobinas Glicadas , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Fatores de Risco , Disfunção Ventricular Esquerda/epidemiologia , Função Ventricular Esquerda , Adulto Jovem
2.
J Biol Chem ; 279(23): 24540-51, 2004 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-15037622

RESUMO

The plant glutathione S-transferase BI-GST has been identified as a potent inhibitor of Bax lethality in yeast, a phenotype associated with oxidative stress and disruption of mitochondrial functions. Screening of a tomato two-hybrid library for BI-GST interacting proteins identified five homologous Tau class GSTs, which readily form heterodimers between them and BI-GST. All six LeGSTUs were found to be able to protect yeast cells from prooxidant-induced cell death. The efficiency of each LeGSTU was prooxidant-specific, indicating a different role for each LeGSTU in the oxidative stress-response mechanism. The prooxidant protective effect of all six proteins was suppressed in the absence of YAP1, a transcription factor that regulates hydroperoxide homeostasis in Saccharomyces cerevisiae, suggesting a role for the LeGSTUs in the context of the YAP1-dependent stress-responsive machinery. The different LeGSTUs exhibited varied substrate specificity and showed activity against oxidative stress by-products, indicating that their prooxidant protective function is likely related to the minimization of oxidative damage. Taken together, these results indicate that Tau class GSTs participate in a broad network of catalytic and regulatory functions involved in the oxidative stress response.


Assuntos
Glutationa Transferase/fisiologia , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-bcl-2 , Sequência de Aminoácidos , Catálise , Dimerização , Relação Dose-Resposta a Droga , Glutationa/química , Glutationa/metabolismo , Dissulfeto de Glutationa/química , Glutationa Transferase/metabolismo , Concentração de Íons de Hidrogênio , Cinética , Solanum lycopersicum/metabolismo , Modelos Moleculares , Dados de Sequência Molecular , Oxidantes/química , Oxidantes/metabolismo , Fenótipo , Testes de Precipitina , Ligação Proteica , Estrutura Secundária de Proteína , Proteínas Proto-Oncogênicas/metabolismo , Saccharomyces cerevisiae/metabolismo , Homologia de Sequência de Aminoácidos , Especificidade por Substrato , Técnicas do Sistema de Duplo-Híbrido , Proteína X Associada a bcl-2
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