scholarly journals Nur77 Coordinately Regulates Expression of Genes Linked to Glucose Metabolism in Skeletal Muscle

2007 ◽  
Vol 21 (9) ◽  
pp. 2152-2163 ◽  
Author(s):  
Lily C. Chao ◽  
Zidong Zhang ◽  
Liming Pei ◽  
Tsugumichi Saito ◽  
Peter Tontonoz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Glucose Metabolism ◽  
Glucose Transporter ◽  
Glucose Utilization ◽  
Glucose Transporter 4 ◽  
Metabolic Gene ◽  
Rat Muscle ◽  
Metabolic Gene Expression

Abstract Innervation is important for normal metabolism in skeletal muscle, including insulin-sensitive glucose uptake. However, the transcription factors that transduce signals from the neuromuscular junction to the nucleus and affect changes in metabolic gene expression are not well defined. We demonstrate here that the orphan nuclear receptor Nur77 is a regulator of gene expression linked to glucose utilization in muscle. In vivo, Nur77 is preferentially expressed in glycolytic compared with oxidative muscle and is responsive to β-adrenergic stimulation. Denervation of rat muscle compromises expression of Nur77 in parallel with that of numerous genes linked to glucose metabolism, including glucose transporter 4 and genes involved in glycolysis, glycogenolysis, and the glycerophosphate shuttle. Ectopic expression of Nur77, either in rat muscle or in C2C12 muscle cells, induces expression of a highly overlapping set of genes, including glucose transporter 4, muscle phosphofructokinase, and glycogen phosphorylase. Furthermore, selective knockdown of Nur77 in rat muscle by small hairpin RNA or genetic deletion of Nur77 in mice reduces the expression of a battery of genes involved in skeletal muscle glucose utilization in vivo. Finally, we show that Nur77 binds the promoter regions of multiple genes involved in glucose metabolism in muscle. These results identify Nur77 as a potential mediator of neuromuscular signaling in the control of metabolic gene expression.

GLUT2 and hexokinase control proximodistal gradient of intestinal glucose metabolism in the newborn pig

1997 ◽  
Vol 272 (6) ◽  
pp. G1530-G1539 ◽  
Author(s):  
C. Cherbuy ◽  
B. Darcy-Vrillon ◽  
L. Posho ◽  
P. Vaugelade ◽  
M. T. Morel ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Glucose Transporter ◽  
Glucose Utilization ◽  
Specific Effect ◽  
Glucose Consumption ◽  
Utilization Rate ◽  
Glucose Turnover ◽  
Proximal Jejunum ◽  
A Site

We have reported previously that a high glycolytic capacity develops soon after birth in enterocytes isolated from suckling newborn pigs. In the present work, we investigated whether such metabolic changes could affect intestinal glucose utilization in vivo and examined possible variations in glucose metabolism along the small intestine. Glucose utilization by individual tissues was assessed using the 2-deoxyglucose technique. The overall glucose utilization rate was doubled in suckling vs. fasting 2-day-old pigs because of significantly higher rates in all tissues studied, except for the brain. In parallel, enterocytes were isolated from the proximal, medium, or distal jejunoileum of newborn vs. 2-day-old pigs and assessed for their capacity to utilize, transport, and phosphorylate glucose. Intestinal glucose consumption accounted for approximately 15% of glucose turnover rate in suckling vs. 8% in fasting pigs. Moreover, there was a proximal-to-distal gradient of glucose utilization in the intestinal mucosa of suckling pigs. Such a gradient was also evidenced on isolated enterocytes. The stimulation of both hexokinase activity (HK2 isoform) and basolateral glucose transporter (GLUT2), as observed in the proximal jejunum, could account for such a site-specific effect of suckling.

scholarly journals Requirement of glucose metabolism for regulation of glucose transporter type 2 (GLUT2) gene expression in liver

1996 ◽  
Vol 314 (3) ◽  
pp. 903-909 ◽  
Author(s):  
Franck RENCUREL ◽  
Gérard WAEBER ◽  
Bénédicte ANTOINE ◽  
Francis ROCCHICCIOLI ◽  
Paulette MAULARD ◽  
...  
Keyword(s):  
Gene Expression ◽  
Glucose Metabolism ◽  
Reporter Gene ◽  
Glucose Transporter ◽  
Regulatory Region ◽  
Proximal Fragment ◽  
Mrna Accumulation ◽  
Glut2 Gene

Previous studies have shown that glucose increases the glucose transporter (GLUT2) mRNA expression in the liver in vivo and in vitro. Here we report an analysis of the effects of glucose metabolism on GLUT2 gene expression. GLUT2 mRNA accumulation by glucose was not due to stabilization of its transcript but rather was a direct effect on gene transcription. A proximal fragment of the 5´ regulatory region of the mouse GLUT2 gene linked to a reporter gene was transiently transfected into liver GLUT2-expressing cells. Glucose stimulated reporter gene expression in these cells, suggesting that glucose-responsive elements were included within the proximal region of the promoter. A dose-dependent effect of glucose on GLUT2 expression was observed over 10 mM glucose irrespective of the hexokinase isozyme (glucokinase Km 16 mM; hexokinase I Km 0.01 mM) present in the cell type used. This suggests that the correlation between extracellular glucose and GLUT2 mRNA concentrations is simply a reflection of an activation of glucose metabolism. The mediators and the mechanism responsible for this response remain to be determined. In conclusion, glucose metabolism is required for the proper induction of the GLUT2 gene in the liver and this effect is transcriptionally regulated.

Skeletal muscle glucose transporter (GLUT-4) protein is decreased in lactating goats

1997 ◽  
Vol 65 (2) ◽  
pp. 257-265 ◽  
Author(s):  
M. Balage ◽  
J. F. Hocquette ◽  
B. Graulet ◽  
P. Ferre ◽  
J. Grizard
Keyword(s):  
Skeletal Muscle ◽  
Protein Content ◽  
Skeletal Muscles ◽  
Glucose Transporter ◽  
Glucose Utilization ◽  
Glut 4 ◽  
Lactating Goats ◽  
Insulin Responsiveness ◽  
Triton X

AbstractLactation in goats is associated with an insulin resistance manifested by an impairment of the ability of insulin maximally to stimulate skeletal muscle glucose utilization. The mechanism responsible for this modification is unknown. Therefore an investigation was made of the insulin-sensitive glucose transporter (GLUT-4) in three skeletal muscles from six lactating (peak of lactation) and six non-lactating goats. GLUT-4 protein content was assessed in crude membrane preparations and Triton X-100 extracts by Western-blot analysis. Lactation resulted in a decrease in GLUT-4 protein content. This decrease was more pronounced in oxidoglycolytic muscles (proportionately -0·40 to -0·60 in m. tensor fasciae latae and longissimus dorsi) than in oxidative muscles (-0·20 in masseter). Down-regulation of the insulin-sensitive glucose transporter (GLUT-4) expression in skeletal muscles from lactating goats may be responsible for the decrease in insulin responsiveness of glucose utilization previously observed in vivo.

scholarly journals Glucose-transporter (GLUT4) protein content in oxidative and glycolytic skeletal muscles from calf and goat

1995 ◽  
Vol 305 (2) ◽  
pp. 465-470 ◽  
Author(s):  
J F Hocquette ◽  
F Bornes ◽  
M Balage ◽  
P Ferre ◽  
J Grizard ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Skeletal Muscles ◽  
Glucose Transporter ◽  
Transporter Protein ◽  
Rat Muscle ◽  
Glucose Transporter Glut4

It is well accepted that skeletal muscle is a major glucose-utilizing tissue and that insulin is able to stimulate in vivo glucose utilization in ruminants as in monogastrics. In order to determine precisely how glucose uptake is controlled in various ruminant muscles, particularly by insulin, this study was designed to investigate in vitro glucose transport and insulin-regulatable glucose-transporter protein (GLUT4) in muscle from calf and goat. Our data demonstrate that glucose transport is the rate-limiting step for glucose uptake in bovine fibre strips, as in rat muscle. Insulin increases the rate of in vitro glucose transport in bovine muscle, but to a lower extent than in rat muscle. A GLUT4-like protein was detected by immunoblot assay in all insulin-responsive tissues from calf and goat (heart, skeletal muscle, adipose tissue) but not in liver, brain, erythrocytes and intestine. Unlike the rat, bovine and goat GLUT4 content is higher in glycolytic and oxido-glycolytic muscles than in oxidative muscles. In conclusion, using both a functional test (insulin stimulation of glucose transport) and an immunological approach, this study demonstrates that ruminant muscles express GLUT4 protein. Our data also suggest that, in ruminants, glucose is the main energy-yielding substrate for glycolytic but not for oxidative muscles, and that insulin responsiveness may be lower in oxidative than in other skeletal muscles.

scholarly journals Electroporated GLUT4‐7 myc ‐GFP detects in vivo glucose transporter 4 translocation in skeletal muscle without discernible changes in GFP patterns

2019 ◽  
Vol 104 (5) ◽  
pp. 704-714 ◽  
Author(s):  
Jonas Roland Knudsen ◽  
Carlos Henriquez‐Olguin ◽  
Zhencheng Li ◽  
Thomas Elbenhardt Jensen
Keyword(s):  
Skeletal Muscle ◽  
Glucose Transporter ◽  
Glucose Transporter 4
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