scholarly journals Restoration of insulin-sensitive glucose transporter (GLUT4) gene expression in muscle cells by the transcriptional coactivator PGC-1

2001 ◽  
Vol 98 (7) ◽  
pp. 3820-3825 ◽  
Author(s):  
L. F. Michael ◽  
Z. Wu ◽  
R. B. Cheatham ◽  
P. Puigserver ◽  
G. Adelmant ◽  
...  
Keyword(s):  
Gene Expression ◽  
Glucose Transporter ◽  
Muscle Cells ◽  
Transcriptional Coactivator ◽  
Glucose Transporter Glut4 ◽  
Glut4 Gene Expression

Transcriptional regulation of the insulin-responsive glucose transporter GLUT4 gene: from physiology to pathology

2008 ◽  
Vol 295 (1) ◽  
pp. E38-E45 ◽  
Author(s):  
Eddy Karnieli ◽  
Michal Armoni
Keyword(s):  
Gene Expression ◽  
Glucose Metabolism ◽  
Glucose Transporter ◽  
Metabolic Demand ◽  
Protein Levels ◽  
Rate Limiting Step ◽  
Glucose Transporter Glut4 ◽  
And Function ◽  
Glut4 Gene Expression

The insulin-responsive glucose transporter 4 (GLUT4) plays a key role in glucose uptake and metabolism in insulin target tissues. Being a rate-limiting step in glucose metabolism, the expression and function of the GLUT4 isoform has been extensively studied and found to be tightly regulated at both mRNA and protein levels. Adaptation to states of enhanced metabolic demand is associated with increased glucose metabolism and GLUT4 gene expression, whereas states of insulin resistance such as type 2 diabetes mellitus (DM2), obesity, and aging are associated with impaired regulation of GLUT4 gene expression and function. The present review focuses on the interplay among hormonal, nutritional, and transcription factors in the regulation of GLUT4 transcription in health and sickness.

scholarly journals Regulation of GLUT4 gene expression by SREBP-1c in adipocytes

2006 ◽  
Vol 399 (1) ◽  
pp. 131-139 ◽  
Author(s):  
Seung-Soon Im ◽  
Sool-Ki Kwon ◽  
Seung-Youn Kang ◽  
Tae-Hyun Kim ◽  
Ha-Il Kim ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Glucose Transporter ◽  
Regulatory Element ◽  
Diabetic Rats ◽  
Dominant Negative ◽  
Luciferase Reporter ◽  
Mrna Levels ◽  
Response Element ◽  
Glut4 Gene Expression

Expression of the GLUT4 (glucose transporter type 4 isoform) gene in adipocytes is subject to hormonal or metabolic control. In the present study, we have characterized an adipose tissue transcription factor that is influenced by fasting/refeeding regimens and insulin. Northern blotting showed that refeeding increased GLUT4 mRNA levels for 24 h in adipose tissue. Consistent with an increased GLUT4 gene expression, the mRNA levels of SREBP (sterol-regulatory-element-binding protein)-1c in adipose tissue were also increased by refeeding. In streptozotocin-induced diabetic rats, insulin treatment increased the mRNA levels of GLUT4 in adipose tissue. Serial deletion, luciferase reporter assays and electrophoretic mobility-shift assay studies indicated that the putative sterol response element is located in the region between bases −109 and −100 of the human GLUT4 promoter. Transduction of the SREBP-1c dominant negative form to differentiated 3T3-L1 adipocytes caused a reduction in the mRNA levels of GLUT4, suggesting that SREBP-1c mediates the transcription of GLUT4. In vivo chromatin immunoprecipitation revealed that refeeding increased the binding of SREBP-1 to the putative sterol-response element in the GLUT4. Furthermore, treating streptozotocin-induced diabetic rats with insulin restored SREBP-1 binding. In addition, we have identified an Sp1 binding site adjacent to the functional sterol-response element in the GLUT4 promoter. The Sp1 site appears to play an additive role in SREBP-1c mediated GLUT4 gene upregulation. These results suggest that upregulation of GLUT4 gene transcription might be directly mediated by SREBP-1c in adipose tissue.

scholarly journals Lipid mediators of insulin resistance: ceramide signalling down-regulates GLUT4 gene transcription in 3T3-L1 adipocytes

1996 ◽  
Vol 319 (1) ◽  
pp. 179-184 ◽  
Author(s):  
Sheree D LONG ◽  
Phillip H PEKALA
Keyword(s):  
Gene Expression ◽  
Mrna Stability ◽  
Glucose Transporter ◽  
Marked Decrease ◽  
Mrna Content ◽  
C6 Ceramide ◽  
Factor Α ◽  
Glucose Transporter Mrna ◽  
Necrosis Factor ◽  
Glut4 Gene Expression

We have previously demonstrated that chronic exposure of 3T3-L1 adipocytes to tumour necrosis factor-α (TNF) resulted in a marked decrease (∼ 90%) in cellular GLUT4 (insulin-responsive glucose transporter) mRNA content as a result of a decreased transcription rate of the GLUT4 gene (∼ 75%) and a reduced half-life of its mRNA (9 to 4.5 h). Investigation of the signalling mechanism responsible for this regulation demonstrated that in the 3T3-L1 adipocytes, sphingomyelin levels decreased to 50% of control levels within 40 min of exposure to TNF, consistent with activation of a sphingomyelinase. In the same manner as with TNF, treatment of the adipocytes with 1-3 µM C6-ceramide, a membrane-permeable analogue of ceramide, decreased GLUT4 mRNA content by ∼ 60%. Subsequent investigations revealed that transcription of the GLUT4 gene was reduced by ∼ 65% in response to C6-ceramide, demonstrating that the decrease in mRNA content is mediated by a reduction in the transcription of the gene. No effect on GLUT4 mRNA stability was observed after exposure of the adipocytes to C6-ceramide. These observations are interesting in light of our previous data demonstrating that TNF affects both GLUT4 transcription and mRNA stability in the 3T3-L1 adipocytes. In conclusion, the effect of ceramide on GLUT4 gene expression is at the level of transcription, suggesting that another pathway controls mRNA stability. These data establish that ceramide-initiated signal transduction pathways exist within the adipocyte, and provide a potential mechanism for control of GLUT4 gene expression.

scholarly journals Effects of steviol on cytotoxicity, adipogenesis, ROS concentration and gene expression in 3T3-L1 Cell Line

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Jakub Kurek ◽  
Joanna Zielińska-Wasielica ◽  
Katarzyna Kowalska ◽  
Anna Olejnik ◽  
Zbigniew Krejpcio
Keyword(s):  
Gene Expression ◽  
Cell Line ◽  
Glucose Transporter ◽  
Stevia Rebaudiana ◽  
Ros Generation ◽  
Steviol Glycosides ◽  
Expression Of Genes ◽  
Intracellular Ros ◽  
Associated Risk Factors ◽  
Glucose Transporter Glut4

AbstractThe increasing prevalence of diabetes mellitus has become one of the world's most serious public health problems. This reflects an increase in associated risk factors such as being overweight or obese. Currently available therapies are associated with a number of adverse effects, so there is a need to search for new substances that can support the treatment.Stevia rebaudiana Bertoni is a plant famous for its sweetness due to the content of steviol glycosides that are derivatives of diterpene – steviol. Stevia and its glycosides are becoming popular in the world of science due to their anti-diabetic potential. However, the mechanisms responsible for its action are not fully understood and require further investigation.The aim of this study was to evaluate the effects of steviol on adipogenesis, intracellular ROS generation and the gene expression, as well as cytotoxicity in murine 3T3-L1 cell line. Cell viability, adipocyte differentiation, intracellular ROS generation and the influence on gene expression in the presence of steviol (in concentrations of 1–100 μM) was determined using MTT assay, Oil Red O staining, NBT methods and RT-PCR. It was found that steviol in concentrations up to 100 μM did not affect proliferation of cells. Also, there were no effects on lipid accumulation and intracellular ROS generation with examined concentrations (0–100 μM). The agent reduced the expression of genes regulating adipogenesis and lipogenesis processes: PPARγ (at concentrations of 10 and 100μM, by 38.1 and 45.3%), C/EBPα (at concentrations of 1, 10 and 100μM, by 36.9, 61.9 and 45.3%), SREBP-1 (at concentrations of 10 and 100μM, by 49.8 and 37.2%), LPL (at concentrations of 1, 10 and 100μM, by 45, 33.7, 30.8%), aP2 (at concentrations of 1, 10 and 100μM, by 36.9, 23.8, 52.4%), FAS (at concentrations of 1, 10 and 100μM, by 55.4, 22.4, 55.6%), LEP (at concentrations of 1, 10 and 100μM, by 27.5, 59.2, 68.6%), ADIPQ (at concentration of 100μM, by 55.6%) and RSTN (at concentrations of 1, 10 and 100μM, by 36.9, 61.9, 63.9%). Steviol lowered the expression of gene coding glucose transporter GLUT4 (at concentrations of 10 and 100μM, by 33.7 and 37.2%).The results of this study seem to confirm that the mechanisms of anti-diabetic effects of steviol may be related to inhibition of expression of genes responsible for adipogenesis, lipogenesis and glucose transport in cells.The presented work is an integral part of the research project(National Science Centre, Poland, NCN 2017/27/B/NZ29/00677)

Ready, set, internalize: mechanisms and regulation of GLUT4 endocytosis

2008 ◽  
Vol 29 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Costin N. Antonescu ◽  
Michelangelo Foti ◽  
Nathalie Sauvonnet ◽  
Amira Klip
Keyword(s):  
Insulin Resistance ◽  
Muscle Contraction ◽  
Glucose Uptake ◽  
Glucose Transporter ◽  
Muscle Cells ◽  
Fat Cells ◽  
Intracellular Membrane ◽  
Membrane Compartments ◽  
Glucose Transporter Glut4

The facilitative glucose transporter GLUT4, a recycling membrane protein, is required for dietary glucose uptake into muscle and fat cells. GLUT4 is also responsible for the increased glucose uptake by myofibres during muscle contraction. Defects in GLUT4 membrane traffic contribute to loss of insulin-stimulated glucose uptake in insulin resistance and Type 2 diabetes. Numerous studies have analysed the intracellular membrane compartments occupied by GLUT4 and the mechanisms by which insulin regulates GLUT4 exocytosis. However, until recently, GLUT4 internalization was less well understood. In the present paper, we review: (i) evidence supporting the co-existence of clathrin-dependent and independent GLUT4 internalization in adipocytes and muscle cells; (ii) the contrasting regulation of GLUT4 internalization by insulin in these cells; and (iii) evidence suggesting regulation of GLUT4 endocytosis in muscle cells by signals associated with muscle contraction.

scholarly journals Glucose transporter 4 gene expression in peripheral blood leukocytes in type 2 diabetes mellitus

2019 ◽  
Vol 12 (1) ◽  
pp. 19-24
Author(s):  
Shahana Jasmin ◽  
Mohammad Ali ◽  
Mokerroma Ferdous ◽  
M. Iqbal Arslan ◽  
Subrata K. Biswas
Keyword(s):  
Gene Expression ◽  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Peripheral Blood ◽  
Glucose Transporter ◽  
Diabetic Patients ◽  
Peripheral Blood Leukocytes ◽  
Blood Leukocytes ◽  
Glut4 Gene Expression

The purpose of this study was to examine the status of glucose transporter type-4 (GLUT4) gene expression in the peripheral blood leukocytes of type 2 diabetic patients and explore the correlation of GLUT4 expression with homeostasis model assessment-insulin resistance with a view to validate GLUT4 as a relatively less invasive alternate marker for insulin resistance. A total of 48 subjects were recruited. Among them, 23 subjects were diabetic and 25 were age, sex and body mass index-matched non-diabetic healthy control subjects. Insulin resistance, beta cell function and insulin sensitivity were assessed from the fasting blood samples. The mRNA levels of GLUT4 gene in the peripheral blood leukocytes were quantified by reverse transcriptase PCR. There was no significant alteration of GLUT4 gene status between type 2 diabetes mellitus and control. The GLUT4 gene expression showed a negative trend in the relationship with fasting glucose, HbA1c, insulin and insulin resistance in diabetic patients. In conclusion, the GLUT4 gene expression in the peripheral blood leukocytes cannot be used as a marker of insulin resistance.

HIF1-α-Mediated Gene Expression Induced by Vitamin B1 Deficiency

2013 ◽  
Vol 83 (3) ◽  
pp. 188-197 ◽  
Author(s):  
Rebecca L. Sweet ◽  
Jason A. Zastre
Keyword(s):  
Gene Expression ◽  
Thiamine Deficiency ◽  
Glucose Transporter ◽  
Neuroblastoma Cell ◽  
Hypoxia Inducible Factor ◽  
Clinical Manifestations ◽  
Vitamin B1 ◽  
Low Oxygen ◽  
Glucose Transporter 1 ◽  
Metabolic Intermediates

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.

Sign in / Sign up

Export Citation Format

Share Document