Glyburide treatment in gestational diabetes is associated with increased placental glucose transporter 1 expression and higher birth weight

Placenta ◽  
2017 ◽  
Vol 57 ◽  
pp. 52-59 ◽  
Author(s):  
Paula Díaz ◽  
Kris Genelyn Dimasuay ◽  
Lindsey Koele-Schmidt ◽  
Brian Jang ◽  
Linda A. Barbour ◽  
...  
2013 ◽  
Vol 83 (3) ◽  
pp. 188-197 ◽  
Author(s):  
Rebecca L. Sweet ◽  
Jason A. Zastre

It is well established that thiamine deficiency results in an excess of metabolic intermediates such as lactate and pyruvate, which is likely due to insufficient levels of cofactor for the function of thiamine-dependent enzymes. When in excess, both pyruvate and lactate can increase the stabilization of the hypoxia-inducible factor 1-alpha (HIF-1α) transcription factor, resulting in the trans-activation of HIF-1α regulated genes independent of low oxygen, termed pseudo-hypoxia. Therefore, the resulting dysfunction in cellular metabolism and accumulation of pyruvate and lactate during thiamine deficiency may facilitate a pseudo-hypoxic state. In order to investigate the possibility of a transcriptional relationship between hypoxia and thiamine deficiency, we measured alterations in metabolic intermediates, HIF-1α stabilization, and gene expression. We found an increase in intracellular pyruvate and extracellular lactate levels after thiamine deficiency exposure to the neuroblastoma cell line SK-N-BE. Similar to cells exposed to hypoxia, there was a corresponding increase in HIF-1α stabilization and activation of target gene expression during thiamine deficiency, including glucose transporter-1 (GLUT1), vascular endothelial growth factor (VEGF), and aldolase A. Both hypoxia and thiamine deficiency exposure resulted in an increase in the expression of the thiamine transporter SLC19A3. These results indicate thiamine deficiency induces HIF-1α-mediated gene expression similar to that observed in hypoxic stress, and may provide evidence for a central transcriptional response associated with the clinical manifestations of thiamine deficiency.


2014 ◽  
Author(s):  
Karolina Stepien ◽  
Sophie Rambihar ◽  
Sue Leigh-Atkins ◽  
Gbemisola Okinoye ◽  
Angelos Kyriacou ◽  
...  

2018 ◽  
Vol 19 (1) ◽  
pp. 26-40 ◽  
Author(s):  
A.P. Alves ◽  
A.C. Mamede ◽  
M.G. Alves ◽  
P.F. Oliveira ◽  
S.M. Rocha ◽  
...  

Hepatocellular carcinoma (HCC) is the most frequently detected primary malignant liver tumor, representing a worldwide public health problem due to its high morbidity and mortality rates. The HCC is commonly detected in advanced stage, precluding the use of treatments with curative intent. For this reason, it is crucial to find effective therapies for HCC. Cancer cells have a high dependence of glycolysis for ATP production, especially under hypoxic environment. Such dependence provides a reliable possible strategy to specifically target cancer cells based on the inhibition of glycolysis. HCC, such as other cancer types, presents a clinically well-known upregulation of several glycolytic key enzymes and proteins, including glucose transporters particularly glucose transporter 1 (GLUT1). Such enzymes and proteins constitute potential targets for therapy. Indeed, for some of these targets, several inhibitors were already reported, such as 2-Deoxyglucose, Imatinib or Flavonoids. Although the inhibition of glycolysis presents a great potential for an anticancer therapy, the development of glycolytic inhibitors as a new class of anticancer agents needs to be more explored. Herein, we propose to summarize, discuss and present an overview on the different approaches to inhibit the glycolytic metabolism in cancer cells, which may be very effective in the treatment of HCC.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Eman M Alfadhli

Abstract Background Maternal obesity and gestational diabetes (GDM) are commonly encountered during pregnancy. Both conditions are independently associated with unfavorable pregnancy consequences. The objective of this study was to compare the effects of obesity and GDM on birth weight, macrosomia, and other adverse pregnancy outcomes. Methods This cohort study involved 531 women with a singleton pregnancy attending the Maternity and Children’s Hospital, Medina, Saudi Arabia, between June 2014 and June 2015. Participants underwent a 75-g oral glucose tolerance test between 24 and 28 weeks. The International Association of Diabetes and Pregnancy Study Groups criteria were used for GDM diagnosis. BMI was assessed at the first antenatal visit, and obesity was defined as a BMI ≥30.0 kg/m2. All women were followed up until delivery. Women were divided into 4 groups: non-GDM nonobese (reference group), GDM nonobese, obese non-GDM, and obese GDM. Clinical characteristics and adverse pregnancy outcomes were compared. Results The mean age and BMI of the participants were 30.5 years and 29.3 kg/m2, respectively. GDM was diagnosed in 50.2% of the participants, and obesity was diagnosed in 47.8% of the participants. Obese women with GDM were the oldest and heaviest among all women. The mean birth weight increased in order among the four groups; it was highest in the infants in the obese GDM group, followed by those in the obese non-GDM, GDM nonobese and reference groups. Obesity and GDM alone or in combination were associated with higher rates of macrosomia and cesarean deliveries than the reference group. Neonatal intensive care unit (NICU) admission was higher in infants in the GDM nonobese and obese GDM groups. The frequency of low Apgar score was significantly higher in infants in the obese GDM group than in infants in the reference group. Conclusions Maternal obesity seems to influence birth weight more than GDM, while GDM is associated with a greater risk of admission to the NICU. The combination of both conditions is associated with the greatest risk of adverse pregnancy outcomes.


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