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1.
Medicine (Baltimore) ; 99(40): e22152, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019392

RESUMO

BACKGROUND: Gestational diabetes mellitus (GDM) produces numerous problems for maternal and fetal outcomes. However, the precise molecular mechanisms of GDM are not clear. METHODS: In our study, we randomly assigned 22 pregnant women with fasting glucose concentrations, 1 hour oral glucose tolerance test (1H-OGTT) and 2 hour oral glucose tolerance test (2H-OGTT), different than 28 normal pregnant women from a sample of 107 pregnant women at the First Affiliated Hospital of Jinan University in China. Lipopolysaccharide (LPS), interleukin 1 alpha (IL-1α), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF-α) were measured from blood plasma of pregnant women and umbilical arteries using ultraviolet spectrophotometry. Hematoxylin & Eosin (H&E), Periodic acid-Schiff (PAS) or Masson staining were performed to examine whether diabetes mellitus altered the morphology of placenta. Quantitative PCR (Q-PCR), western blotting and immunofluorescent staining were performed to examine whether diabetes mellitus and autophagy altered the gene expressions of the placental tissue. RESULTS: We found that women with GDM exhibited increased placental weight and risk of neonatal infection. The concentrations of IL-6 protein and IL-8 protein in GDM were increased in both maternal and umbilical arterial blood. H&E, Masson and PAS staining results showed an increased number of placental villi and glycogen deposition in patients with GDM, but no placental sclerosis was found. Q-PCR results suggested that the expression levels of HIF-1α and the toll like receptor 4 (TLR4)/ myeloid differential protein-88 (MyD88)/ nuclear factor kappa-B (NF-κB) pathway were increased in the GDM placenta. Through Western Blotting, we found that the expression of NF-kappa-B inhibitor alpha (IKBα) and Nuclear factor-κB p65 (NF-κB p65) in GDM placenta was significantly enhanced. We also showed that the key autophagy-related genes, autophagy-related 7 (ATG7) and microtubule-associated protein 1A/1B-light chain 3 (LC3), were increased in GDM compared with normal pregnant women. CONCLUSIONS: Our results suggest that women with GDM exhibit an increased risk of neonatal infection via inflammation and autophagy in the placenta.


Assuntos
Diabetes Gestacional/sangue , Placenta/patologia , Adulto , Diabetes Gestacional/genética , Feminino , Sangue Fetal , Teste de Tolerância a Glucose , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/sangue , Recém-Nascido , Inflamação/sangue , Inflamação/genética , Placenta/microbiologia , Gravidez , Resultado da Gravidez , Receptor 4 Toll-Like/sangue
3.
Yonsei Med J ; 61(9): 780-788, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32882762

RESUMO

PURPOSE: This research was designed to investigate how miR-542-5p regulates the progression of hyperglycemia and hyperlipoidemia. MATERIALS AND METHODS: An in vivo model with diabetic db/db mice and an in vitro model with forskolin/dexamethasone (FSK/DEX)-induced primary hepatocytes and HepG2 cells were employed in the study. Bioinformatics analysis was conducted to identify the expression of candidate miRNAs in the liver tissues of diabetic and control mice. H&E staining revealed liver morphology in diabetic and control mice. Pyruvate tolerance tests, insulin tolerance tests, and intraperitoneal glucose tolerance test were utilized to assess insulin resistance. ELISA was conducted to evaluate blood glucose and insulin levels. Red oil O staining showed lipid deposition in liver tissues. Luciferase reporter assay was used to depict binding between miR-542-5p and forkhead box O1 (FOXO1). RESULTS: MiR-542-5p expression was under-expressed in the livers of db/db mice. Further in vitro experiments revealed that FSK/DEX, which mimics the effects of glucagon and glucocorticoids, induced cellular glucose production in HepG2 cells and in primary hepatocytes cells. Notably, these changes were reversed by miR-542-5p. We found that transcription factor FOXO1 is a target of miR-542-5p. Further in vivo study indicated that miR-542-5p overexpression decreases FOXO1 expression, thereby reversing increases in blood glucose, blood lipids, and glucose-related enzymes in diabetic db/db mice. In contrast, anti-miR-542-5p exerted an adverse influence on blood glucose and blood lipid metabolism, and its stimulatory effects were significantly inhibited by sh-FOXO1 in normal control mice. CONCLUSION: Collectively, our results indicated that miR-542-5p inhibits hyperglycemia and hyperlipoidemia by targeting FOXO1.


Assuntos
Diabetes Mellitus Tipo 2/genética , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O1/metabolismo , Hiperglicemia/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , MicroRNAs/genética , Animais , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Regulação da Expressão Gênica , Glucose/metabolismo , Teste de Tolerância a Glucose , Células Hep G2 , Hepatócitos/metabolismo , Humanos , Hiperglicemia/metabolismo , Hiperlipidemias/metabolismo , Resistência à Insulina , Metabolismo dos Lipídeos , Fígado/metabolismo , Camundongos , MicroRNAs/metabolismo , MicroRNAs/farmacologia
7.
Zhonghua Yu Fang Yi Xue Za Zhi ; 54(9): 968-973, 2020 Sep 06.
Artigo em Chinês | MEDLINE | ID: mdl-32907287

RESUMO

Objective: To estimate the effect of comorbid gestational diabetes mellitus (GDM) and depression on glucose metabolism and neonatal morphology. Methods: From March 2015 to October 2018, recruited 18 to 28 weeks pregnant women who met the criteria in the Hefei First People's Hospital or First Affiliated Hospital of Anhui Medical University or Anhui Maternal and Child Health Hospital, including a total of 4 380 study subjects, of which the birth outcome information of 3 827 newborns were collected. The self-made questionnaire "Maternal Health Questionnaire for Hefei City" and Edinburgh Postpartum Depression Scale were used to obtain basic demographic characteristics and emotional state of depression. Data from the 75-g oral-glucose-tolerance test were obtained at 24-28 weeks of gestation. After delivery, delivery outcome information were collected from the hospital medical records. Covariance analysis was used to analyze the differences in glucose metabolism indicators and neonatal outcome indicators in pregnant women with different GDM and depression status. Multiple logistic regression model was used to analyze the correlation between GDM and depression, with different groups of GDM and depression status (no GDM and depression, simple depression, simple GDM, comorbid GDM and depression)as independent variables and whether they were large for gestational age as dependent variables. The interaction between GDM and depression was also analyzed. Results: The 4 380 pregnant women were (28.8±4.2) years old. The incidence of GDM was 19.5% (852/4 380), and the detection rates of depression in the second and third trimesters were 12.1% (526/4 380) and 12.3% (536/4 367). PG-1h and AUC in the comorbid GDM and depression group were significantly higher than those in the group with no GDM and depression (P<0.05) and the single GDM group (P<0.05). After adjusting for factors such as the childbirth age, education level, family's main economic income, BMI before pregnancy, parity, number of physical activities, and weight gain during pregnancy, compared with the group with no GDM and depression, the RR(95%CI) of LGA occurred in the single depression group, the single GDM group and the comorbid group were 1.31(0.89-1.91), 1.51(1.14-2.00) and 2.43(1.29-4.57), respectively. Further analysis showed that the association between GDM pregnant women with depression and newborn LGA ï¼»RR (95%CI): 2.12 (1.01-4.49)ï¼½ was stronger than that between GDM pregnant women without depression and newborn LGA ï¼»RR (95%CI): 1.50 (1.12-1.99)ï¼½, the P interaction value was<0.05. Conclusion: The status of comorbid GDM and depression can impair glucose metabolism and increase the risk of LGA.


Assuntos
Diabetes Gestacional/epidemiologia , Adulto , Criança , Depressão/epidemiologia , Feminino , Glucose , Teste de Tolerância a Glucose , Humanos , Recém-Nascido , Gravidez , Resultado da Gravidez , Ganho de Peso , Adulto Jovem
8.
J Assoc Physicians India ; 68(8): 43-46, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32738840

RESUMO

Objectives: The aim of the present study was to assess the glycemic status measured as Fasting Plasma Glucose (FPG) and glycosylated haemoglobin (A1C); prevalence of Insulin Resistance (IR), hypogonadism and to study their correlation with CD4 (CD4 lymphocyte) counts in HIV infected patients receiving ART. Correlation between percentage android fat and IR was also studied. Methods and materials: 84 HIV male patients as diagnosed by ELISA test aged 18 to 70 years were included in this case control study. Software IBM SPSS 20.1 and Microsoft Excel 2013 was used for analysis of data. The numerical data was compared using two tailed student t-test. Log transformation was used for the conversion of qualitative data (% android fat) to quantitative data so that it can be correlated to HOMA-IR. The level of significance was considered 0.05. Results: Out of total 84 patients, 19 had FPG ≥ 100. 11(13%) had Impaired Fasting Glucose (IFG) and 8 (9.5%) had Diabetes Mellitus (DM). 20 patients had A1C > 5.6. Nine (10.7%) patients had Impaired Glucose Tolerance (IGT) and 11 (13.1%) patients had DM on the basis of A1C. 11 (13.1%) patients had DM based on either FPG or A1C criteria. Patients with higher percentage android fat had significantly higher IR. 33 (39%) patients had hypogonadism, six patients (7.1%) had primary hypogonadism; 24 (28.6%) had secondary hypogonadism and 3 (3.6 %) had compensatory hypogonadism. Conclusion: Patients with lower CD4 counts had significantly higher dysglycemia and IR. Serum testosterone levels were progressively lower (insignificant) with decreasing CD4 counts.


Assuntos
Diabetes Mellitus Tipo 2 , Intolerância à Glucose , Infecções por HIV , Hipogonadismo , Resistência à Insulina , Adolescente , Adulto , Idoso , Glicemia , Estudos de Casos e Controles , Jejum , Teste de Tolerância a Glucose , Humanos , Insulina , Masculino , Pessoa de Meia-Idade , Adulto Jovem
9.
Diabetes Res Clin Pract ; 167: 108353, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32739381

RESUMO

AIMS: We assessed how altered diagnostic processes and criteria for gestational diabetes mellitus (GDM) recommended by the United Kingdom (UK), Canada and Australia for use during the COVID-19 pandemic would affect both GDM frequency and related adverse outcomes. METHODS: Secondary analysis of 5974 HAPO study women with singleton pregnancies who underwent 75 g OGTTs and HbA1c assays between 24 and 32 weeks' gestation and who received no treatment for GDM. RESULTS: All post COVID-19 modified pathways reduced GDM frequency - UK (81%), Canada (82%) and Australia (25%). Canadian women whose GDM would remain undetected post COVID-19 (missed GDMs) displayed similar rates of pregnancy complications to those with post COVID-19 GDM. Using UK modifications, the missed GDM group were at slightly lower risk whilst the women missed using the Australian modifications were at substantially lower risk. CONCLUSIONS: The modifications in GDM diagnosis proposed for the UK, Canada and Australia result in differing reductions of GDM frequency. Each has both potential benefits in terms of reduction in potential exposure to COVID-19 and costs in terms of missed opportunities to influence pregnancy and postpartum outcomes. These factors should be considered when deciding which protocol is most appropriate for a particular context.


Assuntos
Glicemia/metabolismo , Infecções por Coronavirus/prevenção & controle , Diabetes Gestacional/diagnóstico , Teste de Tolerância a Glucose/métodos , Diagnóstico Ausente/estatística & dados numéricos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Complicações Infecciosas na Gravidez/prevenção & controle , Adulto , Austrália , Betacoronavirus , Canadá , Diabetes Gestacional/metabolismo , Jejum , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Guias de Prática Clínica como Assunto , Gravidez , Resultado da Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Reino Unido
10.
Niger J Clin Pract ; 23(8): 1087-1094, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32788486

RESUMO

Background: Maternal hyperglycemia first diagnosed in pregnancy, previously referred to as gestational diabetes mellitus is associated with health consequences for both the mother and her fetus/baby, not only in the short term but also in the long term. Early screening helps to identify women with overt diabetes or those with early onset GDM. Aims: The aim of this study was to determine the diagnostic performance of two screening tests (Random plasma glucose, Random capillary glucose) in relation to 75g Oral glucose tolerance test (OGTT) done before 24 weeks gestation. Methods: This prospective longitudinal cohort study was carried out between 1st February, 2017 and 31st July, 2017, at two teaching hospitals in Nigeria. Two hundred and eighty one (281) pregnant women who met the inclusion criteria were selected and screened with both random plasma glucose (RPG) and random capillary glucose (RCG) before 24 weeks of pregnancy. They were then made to undergo 75g OGTT a week later. The diagnostic performance of the screening tests were determined. Results: A total of 270 women had 75g OG. Conclusion: Random plasma glucose and Random capillary glucose performed poorly compared to 75g-OGTT in detecting hyperglycemia in early pregnancy.


Assuntos
Glicemia/análise , Diabetes Gestacional/sangue , Diabetes Gestacional/diagnóstico , Teste de Tolerância a Glucose/métodos , Hiperglicemia/diagnóstico , Programas de Rastreamento/métodos , Adulto , Feminino , Humanos , Hiperglicemia/sangue , Estudos Longitudinais , Nigéria/epidemiologia , Gravidez , Primeiro Trimestre da Gravidez , Segundo Trimestre da Gravidez , Gestantes , Prevalência , Estudos Prospectivos , Reprodutibilidade dos Testes
11.
PLoS One ; 15(8): e0237224, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32817647

RESUMO

AIM: The addition of maternal age to fasting plasma glucose (FPG) at 24-28 gestational weeks improves the performance of GDM screening as maternal age increases. However, this method delays the diagnosis of GDM. Since FPG at the first prenatal visit (FPV) is a screening option for pre-existing diabetes, we evaluated the performance of age plus FPG at the FPV to reduce the need for the OGTT. METHODS: Pregnant women were recruited consecutively in 2013-2018 (the training cohort) and 2019 (the validation cohort). We excluded women with twin pregnancies, unavailable FPG at the FPV or OGTT data, pre-pregnancy diabetes, or a history of GDM. All participants underwent FPG and haemoglobin A1c (HbA1c) at the FPV and received 75-g OGTT at 24-28 gestational weeks if FPG at the FPV was <92 mg/dL. GDM was diagnosed by the IADPSG criteria. Two algorithms were developed with the cutoffs determined when the percentage requiring OGTT (OGTT%) was the lowest and the sensitivity was ≥90%. RESULTS: The incidence of GDM increased with age. The "FPG at the FPV" algorithm reduced OGTT% to 68.8% with the FPG cutoff at 79 mg/dl. The "age plus FPG at the FPV" algorithm, with the cutoff of 114, further reduced OGTT% to 58.3%, with the sensitivity of 90.7% (9.3% GDM missed) and the specificity of 100%. These findings were replicated in the validation cohort. CONCLUSIONS: Screening GDM by maternal age plus FPG at the FPV can reduce OGTT%, especially in populations with a significant proportion of pregnant women with advanced ages.


Assuntos
Glicemia/análise , Diabetes Gestacional/sangue , Adulto , Diabetes Gestacional/diagnóstico , Jejum/sangue , Feminino , Teste de Tolerância a Glucose , Hemoglobina A Glicada/análise , Humanos , Programas de Rastreamento , Idade Materna , Gravidez , Estudos Prospectivos
12.
Diabetes Res Clin Pract ; 167: 108353, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: covidwho-688787

RESUMO

AIMS: We assessed how altered diagnostic processes and criteria for gestational diabetes mellitus (GDM) recommended by the United Kingdom (UK), Canada and Australia for use during the COVID-19 pandemic would affect both GDM frequency and related adverse outcomes. METHODS: Secondary analysis of 5974 HAPO study women with singleton pregnancies who underwent 75 g OGTTs and HbA1c assays between 24 and 32 weeks' gestation and who received no treatment for GDM. RESULTS: All post COVID-19 modified pathways reduced GDM frequency - UK (81%), Canada (82%) and Australia (25%). Canadian women whose GDM would remain undetected post COVID-19 (missed GDMs) displayed similar rates of pregnancy complications to those with post COVID-19 GDM. Using UK modifications, the missed GDM group were at slightly lower risk whilst the women missed using the Australian modifications were at substantially lower risk. CONCLUSIONS: The modifications in GDM diagnosis proposed for the UK, Canada and Australia result in differing reductions of GDM frequency. Each has both potential benefits in terms of reduction in potential exposure to COVID-19 and costs in terms of missed opportunities to influence pregnancy and postpartum outcomes. These factors should be considered when deciding which protocol is most appropriate for a particular context.


Assuntos
Glicemia/metabolismo , Infecções por Coronavirus/prevenção & controle , Diabetes Gestacional/diagnóstico , Teste de Tolerância a Glucose/métodos , Diagnóstico Ausente/estatística & dados numéricos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Complicações Infecciosas na Gravidez/prevenção & controle , Adulto , Austrália , Betacoronavirus , Canadá , Diabetes Gestacional/metabolismo , Jejum , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Guias de Prática Clínica como Assunto , Gravidez , Resultado da Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Reino Unido
14.
Nat Commun ; 11(1): 3755, 2020 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-32709874

RESUMO

Obesity is associated with low-grade chronic inflammation promoting insulin-resistance and diabetes. Gut microbiota dysbiosis is a consequence as well as a driver of obesity and diabetes. Mucosal-associated invariant T cells (MAIT) are innate-like T cells expressing a semi-invariant T cell receptor restricted to the non-classical MHC class I molecule MR1 presenting bacterial ligands. Here we show that during obesity MAIT cells promote inflammation in both adipose tissue and ileum, leading to insulin resistance and impaired glucose and lipid metabolism. MAIT cells act in adipose tissue by inducing M1 macrophage polarization in an MR1-dependent manner and in the gut by inducing microbiota dysbiosis and loss of gut integrity. Both MAIT cell-induced tissue alterations contribute to metabolic dysfunction. Treatment with MAIT cell inhibitory ligand demonstrates its potential as a strategy against inflammation, dysbiosis and metabolic disorders.


Assuntos
Disbiose/imunologia , Inflamação/patologia , Intestinos/patologia , Células T Invariáveis Associadas à Mucosa/patologia , Obesidade/metabolismo , Tecido Adiposo/patologia , Animais , Citocinas/genética , Citocinas/metabolismo , Dieta Hiperlipídica , Disbiose/complicações , Microbioma Gastrointestinal , Teste de Tolerância a Glucose , Íleo/patologia , Inflamação/complicações , Mucosa Intestinal/patologia , Intestinos/diagnóstico por imagem , Ligantes , Contagem de Linfócitos , Macrófagos/metabolismo , Imagem por Ressonância Magnética , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/complicações , Obesidade/diagnóstico por imagem , Fenótipo , Pterinas/farmacologia , Receptores de Antígenos de Linfócitos T/metabolismo
15.
S Afr Med J ; 110(2): 154-158, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-32657688

RESUMO

BACKGROUND: Gestational diabetes mellitus (GDM), a disorder of glucose intolerance first encountered during pregnancy, has far-reaching implications for both mother and child. Insulin therapy remains the 'gold standard' of care, with oral hypoglycaemic agents (OHAs) increasingly being viewed as potential alternatives. OBJECTIVES: To compare maternal and neonatal outcomes in two cohorts of women with GDM exposed to either insulin monotherapy or OHAs. METHODS: A retrospective medical record review at Chris Hani Baragwanath Academic Hospital in South Africa was conducted for women with GDM diagnosed using the 100 g oral glucose tolerance test and/or random capillary blood glucose >11.1 mmol/L in 2010 - 2014. The findings were compared with a previous audit at the same clinic for the period 1992 - 2002. Variables of interest included maternal demographics, maternal comorbidities, glycaemic indices, treatments used during pregnancy, and obstetric and neonatal outcomes. RESULTS: A total of 192 women with GDM were identified for 2010 - 2014, and there were 348 women in the previous audit (1992 - 2002). Baseline characteristics and outcomes of women in the two cohorts were similar apart from earlier presentation (mean (standard deviation) gestational age (GA) 27 (7.5) weeks v. 28.3 (6.4) weeks; p=0.04), lower GA at delivery (36.3 (3.6) weeks v. 37 (1.6) weeks); p=0.008) and lower macrosomia rates (12.5% v. 4.9%; p=0.011) in the later cohort. When comparing the individual OHAs against insulin in the later cohort, both agents were comparable to insulin in terms of maternal and neonatal outcomes. CONCLUSIONS: This study contributes to the paucity of data on the safety of OHAs in GDM pregnancy in terms of maternal and neonatal outcomes. OHAs were shown to be an effective alternative to insulin for women with GDM in whom lifestyle measures fail, particularly in a resource-poor setting.


Assuntos
Diabetes Gestacional/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Resultado da Gravidez , Administração Oral , Adulto , Estudos de Coortes , Feminino , Macrossomia Fetal/epidemiologia , Teste de Tolerância a Glucose , Humanos , Recém-Nascido , Gravidez , Estudos Retrospectivos , África do Sul
16.
Nutr Metab Cardiovasc Dis ; 30(9): 1418-1422, 2020 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-32675009

RESUMO

AIM: In response to the COVID-19 pandemic, there is a need for substantial changes in the procedures for accessing healthcare services. Even in the current pandemic, we should not reduce our attention towards the diagnosis and treatment of GDM. The purpose of this document is to provide a temporary guide for GDM screening, replacing the current guidelines when it is not possible to implement standard GDM screening because of an unfavorable risk/benefit ratio for pregnant women or when usual laboratory facilities are not available. DATA SYNTHESIS: At the first visit during pregnancy, we must exclude the presence of "Overt diabetes" in all women. The criteria for the diagnosis of overt diabetes are either fasting plasma glucose ≥126 mg/dL, or random plasma glucose ≥200 mg/dL, or glycated hemoglobin ≥6.5%. When the screening procedure (OGTT) cannot be safely performed, the diagnosis of GDM is acceptable if fasting plasma glucose is ≥ 92 mg/dL. In order to consider the impaired fasting glucose as an acceptable surrogate for the diagnosis of GDM, the fasting glucose measurement should be performed within the recommended time windows for the risk level (high or medium risk). CONCLUSIONS: The changes to the screening procedure for GDM reported below are specifically produced in response to the health emergency of the COVID-19 pandemic. Therefore, these recommended changes should cease to be in effect and should be replaced by current national guidelines when the healthcare authorities declare the end of this emergency.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Diabetes Gestacional/diagnóstico , Pneumonia Viral/epidemiologia , Glicemia/análise , Feminino , Teste de Tolerância a Glucose , Humanos , Itália , Pandemias , Gravidez
17.
PLoS One ; 15(7): e0235913, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32673349

RESUMO

In mammals, inter- and intraspecies differences in consumption of sweeteners largely depend on allelic variation of the Tas1r3 gene (locus Sac) encoding the T1R3 protein, a sweet taste receptor subunit. To assess the influence of Tas1r3 polymorphisms on feeding behavior and metabolism, we examined the phenotype of F1 male hybrids obtained from crosses between the following inbred mouse strains: females from 129SvPasCrl (129S2) bearing the recessive Tas1r3 allele and males from either C57BL/6J (B6), carrying the dominant allele, or the Tas1r3-gene knockout strain C57BL/6J-Tas1r3tm1Rfm (B6-Tas1r3-/-). The hybrids 129S2B6F1 and 129S2B6-Tas1r3-/-F1 had identical background genotypes and different sets of Tas1r3 alleles. The effect of Tas1r3 hemizygosity was analyzed by comparing the parental strain B6 (Tas1r3 homozygote) and hemizygous F1 hybrids B6 × B6-Tas1r3-/-. Data showed that, in 129S2B6-Tas1r3-/-F1 hybrids, the reduction of glucose tolerance, along with lower consumption of and lower preference for sweeteners during the initial licking responses, is due to expression of the recessive Tas1r3 allele. Hemizygosity of Tas1r3 did not influence these behavioral and metabolic traits. However, the loss of the functional Tas1r3 allele was associated with a small decline in the long-term intake and preference for sweeteners and reduction of plasma insulin and body, liver, and fat mass.


Assuntos
Glucose/metabolismo , Receptores Acoplados a Proteínas-G/genética , Paladar/fisiologia , Alelos , Animais , Feminino , Preferências Alimentares , Genótipo , Teste de Tolerância a Glucose , Hemizigoto , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fenótipo , Polimorfismo Genético , Receptores Acoplados a Proteínas-G/deficiência
18.
Sci Total Environ ; 744: 140994, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-32717465

RESUMO

INTRODUCTION: Environmental temperature has been described to affect plasma glucose levels after oral glucose tolerance testing (OGTT). AIMS: We evaluated the relationship between seasons and environmental temperature and gestational diabetes mellitus (GDM) diagnosis and treatment. METHODS: We analyzed data from 2374 women retrospectively. GDM was diagnosed in 473 patients by a 100-g OGTT. OGTT results and needing of insulin therapy were evaluated in relation to seasons and environmental temperature (mean temperature and temperature change) the day of the OGTT and the preceding 14 and 28 days. RESULTS: We found significant seasonal differences in the percentage of GDM: 24.4% in summer vs. 15.6% in autumn (p < 0.01). The odds ratio (OR) for being diagnosed with GDM was 1.78 in summer relative to autumn, after controlling for age. A higher mean temperature the day of the OGTT and the preceding 14 and 28 days increased the risk of being diagnosed with GDM the months in which temperature was rising (March-August) but not the months in which temperature was decreasing (September-February). We observed a negative correlation between temperature and fasting glucose and a positive correlation with post-load glucose. Neither the season nor the environmental temperature affected the risk of requiring insulin therapy. CONCLUSIONS: There is a higher prevalence of GDM diagnosis at warmer seasons and at rising temperatures the 2-4 weeks prior to the OGTT. The impact of temperature is different between fasting and post-load glucose.


Assuntos
Diabetes Gestacional , Glicemia , Feminino , Teste de Tolerância a Glucose , Humanos , Gravidez , Estudos Retrospectivos , Temperatura
19.
Life Sci ; 257: 118118, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32702445

RESUMO

AIMS: Recent findings have instituted the role of hyperglycemia-related AGE/RAGE and NF-κB in instigating reactive oxygen species (ROS) mediated mitochondrial dysfunction and apoptosis of hepatocyte, which leads to steatohepatitis. Naringin, a flavanone glycoside found to possess myriads of pharmacological benefits along with its antioxidant and anti-inflammatory properties. Consequently, we aimed to decipher the effect of naringin on RAGE/NF-κB mediated mitochondrial apoptosis in type 2 diabetes mellitus (T2DM)-induced steatohepatitis. MAIN METHODS: Hepatic HepG2 cells were cultured in palmitic acid medium with and without naringin. Lipid content was examined by Oil Red O and Nile Red staining. Cellular apoptosis was determined by Annexin V-FITC/PI staining. An experimental T2DM-induced steatohepatitis was developed in Sprague Dawley rats by high-fat diet (HFD) for 12 weeks. The naringin was administrated orally at a dose of 100 mg/kg, daily for eight weeks. Glucose and insulin tolerance test was performed. Liver sections were stained by hematoxylin-eosin and picrosirius red. The mRNA and protein expression of RAGE and NF-κB were determined by qPCR, Immunofluorescence, and Immunoblotting. Mitochondrial membrane potential (MMP), cellular and mitochondrial ROS were measured by FACS. KEY FINDINGS: Palmitic acid encountered HepG2 cells and HFD fed rats exhibited hyperlipidemia, insulin resistance, abnormal aminotransferases, steatosis, and fibrosis. Besides, the level of AGEs, RAGE, NF-κB, and oxidative stress were exacerbated. Moreover, MMP, cellular and mitochondrial ROS were altered in diabetic rats. Nevertheless, the naringin treatment ameliorated the steatohepatitis by improving the levels of aforementioned parameters. SIGNIFICANCE: Collectively, these findings suggested anti-steatohepatitis potential of naringin in diabetics.


Assuntos
Antioxidantes/uso terapêutico , Apoptose/efeitos dos fármacos , Diabetes Mellitus Tipo 2/complicações , Fígado Gorduroso/tratamento farmacológico , Flavanonas/uso terapêutico , Mitocôndrias/efeitos dos fármacos , NF-kappa B/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Animais , Diabetes Mellitus Experimental/complicações , Fígado Gorduroso/etiologia , Fígado Gorduroso/patologia , Imunofluorescência , Teste de Tolerância a Glucose , Células Hep G2/efeitos dos fármacos , Humanos , Insulina/sangue , Fígado/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real
20.
Life Sci ; 257: 118127, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32707052

RESUMO

BACKGROUND: Cigarette smoking or nicotine replacement therapy has been associated with cardiometabolic disorders (CMD). Hyperuricemia has been implicated in the pathogenesis of CMD and cardiorenal dysfunction. Gut microbiota-derived short chain fatty acids (SCFAs) have been reported to have beneficial glucoregulatory and cardiorenal protective effects. This study aimed at investigating the effect of acetate, a gut-derived SCFA, on nicotine-induced CMD and associated cardiorenal dysmetabolism. MATERIALS AND METHOD: Twenty-four male Wistar rats (n = 6/group) were grouped as: vehicle (p.o.), nicotine-exposed (1.0 mg/kg; p.o.), and sodium acetate-treated (200 mg/kg; p.o.) with or without nicotine exposure daily for 6 weeks. Glucose regulation was evaluated by oral glucose tolerance test and homeostatic model assessment of insulin resistance. Cardiac and renal triacylglycerol (TG), lactate, nitric oxide (NO), uric acid (UA) levels, lactate dehydrogenase (LDH), creatine kinase (CK), adenosine deaminase (ADA), and xanthine oxidase (XO) activities were measured. RESULTS: The CMD were confirmed in the nicotine-exposed rats that exhibited lower body weight, insulin resistance, endothelial dysfunction, glucose intolerance, increased cardiac and renal TG, TG/HDL-cholesterol, UA, lactate, lipid peroxidation, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, LDH, CK, ADA and XO activities. Concurrent treatment with acetate prevented nicotine-induced glucometabolic and cardiorenal alterations. CONCLUSION: In summary, these results implied that nicotine exposure caused glucometabolic dysregulation and surplus lipid deposit in the heart and kidney through increased UA production and CK activity. Therefore, oral acetate administration prevents cardiorenal lipotoxicity and glucometabolic dysregulation via suppression of UA production and CK activity in nicotine-exposed rats.


Assuntos
Creatina Quinase/metabolismo , Coração/efeitos dos fármacos , Rim/efeitos dos fármacos , Redes e Vias Metabólicas/efeitos dos fármacos , Miocárdio/metabolismo , Nicotina/efeitos adversos , Acetato de Sódio/farmacologia , Ácido Úrico/metabolismo , Animais , Glucose/metabolismo , Teste de Tolerância a Glucose , Resistência à Insulina , Rim/metabolismo , Masculino , Nicotina/antagonistas & inibidores , Ratos , Ratos Wistar
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