Thioredoxin interacting protein mediates lipid-induced impairment of glucose uptake in skeletal muscle

2016 ◽  
Vol 479 (4) ◽  
pp. 933-939 ◽  
Author(s):  
Ashok Mandala ◽  
Nabanita Das ◽  
Sudarshan Bhattacharjee ◽  
Bidisha Mukherjee ◽  
Satinath Mukhopadhyay ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Interacting Protein ◽  
Thioredoxin Interacting Protein

scholarly journals Immobilization rapidly induces thioredoxin-interacting protein gene expression together with insulin resistance in rat skeletal muscle

2018 ◽  
Vol 125 (2) ◽  
pp. 596-604 ◽  
Author(s):  
Emi Kawamoto ◽  
Keigo Tamakoshi ◽  
Song-Gyu Ra ◽  
Hiroyuki Masuda ◽  
Kentaro Kawanaka
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Protein Expression ◽  
Glucose Uptake ◽  
Rapid Development ◽  
Plaster Cast ◽  
Interacting Protein ◽  
Thioredoxin Interacting Protein ◽  
Transcription Inhibitor ◽  
Male Wistar Rats

Acute short duration of disuse induces the development of insulin resistance for glucose uptake in rodent skeletal muscle. Because thioredoxin-interacting protein (TXNIP) has been implicated in the downregulation of insulin signaling and glucose uptake, we examined the possibility that muscle disuse rapidly induces insulin resistance via increased TXNIP mRNA and protein expression. Male Wistar rats were subjected to unilateral 6-h hindlimb immobilization by plaster cast. At the end of this period, the soleus muscles from both immobilized and contralateral nonimmobilized hindlimbs were excised and examined. The 6-h immobilization resulted in an increase in TXNIP mRNA and protein expressions together with a decrease in insulin-stimulated 2-deoxyglucose uptake in the rat soleus muscle. Additionally, in the rats euthanized 6 h after the plaster cast removal, TXNIP protein expression and insulin-stimulated glucose uptake in the immobilized muscle had both been restored to a normal level. Various interventions (pretreatment with transcription inhibitor actinomycin D or AMP-dependent protein kinase activator 5-aminoimidazole-4-carboxamide ribonucleotide) also suppressed the increase in TXNIP protein expression in 6-h-immobilized muscle together with partial prevention of insulin resistance for glucose uptake. These results suggested the possibility that increased TXNIP protein expression in immobilized rat soleus muscles was associated with the rapid induction of insulin resistance for glucose uptake in that tissue. NEW & NOTEWORTHY The cellular mechanism by which disuse rapidly induces muscle insulin resistance for glucose uptake remains to be identified. Using a rat hindlimb immobilization model, our findings suggest the possibility that transcriptional upregulation of thioredoxin-interacting protein is associated with the immobilization-induced rapid development of insulin resistance in skeletal muscle.

scholarly journals MondoA-Mlx Transcriptional Activity Is Limited by mTOR-MondoA Interaction

2014 ◽  
Vol 35 (1) ◽  
pp. 101-110 ◽  
Author(s):  
Mohan R. Kaadige ◽  
Jingye Yang ◽  
Blake R. Wilde ◽  
Donald E. Ayer
Keyword(s):  
Glucose Uptake ◽  
Leucine Zipper ◽  
Aerobic Glycolysis ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Inhibitors ◽  
Nutrient Status ◽  
Regulatory Relationship ◽  
Interacting Protein ◽  
Thioredoxin Interacting Protein ◽  
Helix Loop Helix

Mammalian target of rapamycin (mTOR) integrates multiple signals, including nutrient status, growth factor availability, and stress, to regulate cellular and organismal growth. How mTOR regulates transcriptional programs in response to these diverse stimuli is poorly understood. MondoA and its obligate transcription partner Mlx are basic helix-loop-helix leucine zipper (bHLHZip) transcription factors that sense and execute a glucose-responsive transcriptional program. MondoA-Mlx complexes activate expression of thioredoxin-interacting protein (TXNIP), which is a potent inhibitor of cellular glucose uptake and aerobic glycolysis. Both mTOR and MondoA are central regulators of glucose metabolism, yet whether they interact physically or functionally is unknown. We show that inhibition of mTOR induces MondoA-dependent expression of TXNIP, coinciding with reduced glucose uptake. Mechanistically, mTOR binds to MondoA in the cytoplasm and prevents MondoA-Mlx complex formation, restricting MondoA's nuclear entry and reducing TXNIP expression. Further, we show that mTOR inhibitors and reactive oxygen species (ROS) regulate interaction between MondoA and mTOR in an opposing manner. Like mTOR's suppression of the MondoA-TXNIP axis, MondoA can also suppress mTOR complex 1 (mTORC1) activity via its direct transcriptional regulation of TXNIP. Collectively, these studies reveal a regulatory relationship between mTOR and the MondoA-TXNIP axis that we propose contributes to glucose homeostasis.

Abstract 108: Thioredoxin-interacting Protein Interacts with Glucose Transporters to Regulate Cardiac Glucose Metabolism

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Bing F Wang ◽  
Ronald B Myers ◽  
Gregory M Fomovsky ◽  
Samuel Lee ◽  
Parth Patwari ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Glucose Transporters ◽  
Cardiac Response ◽  
Diabetic Mice ◽  
Adrenergic Stimulation ◽  
Functional Reserve ◽  
Interacting Protein ◽  
Thioredoxin Interacting Protein

A change in basal glucose transport into skeletal muscle, heart, and adipose is a critical feature of insulin resistance and diabetes. Glucose transport is tightly regulated by a protein family of glucose transporters (GLUTs). Thus, defining how cardiomyocytes adapt to changes in extracellular and intracellular glucose concentrations by recruiting GLUTs is crucial to understanding cardiac metabolism under both normal and diabetic conditions. Thioredoxin-Interacting Protein (Txnip), originally characterized as a binding partner of antioxidant thioredoxin, is now known to be a member of the arrestin protein superfamily. We have previously shown that glucose uptake is robustly enhanced in Txnip-knockout hearts; however, the precise mechanism for this effect remains elusive. Here, we present a novel feedback mechanism by which Txnip controls glucose metabolism. High glucose levels induced Txnip expression in rat cardiomyocytes in vitro and in the myocardium of streptozotocin (STZ)-induced diabetic mice in vivo. Our proteomic and functional analyses found that Txnip directly interacts with GLUT1 and GLUT4 and strikingly inhibits cellular glucose uptake through direct interactions with GLUTs. Using inducible cardiac-specific deletion of Txnip (Txnip-CKO), we further demonstrated that Txnip plays a functional role in STZ-induced diabetic cardiomyopathy. While β-adrenergic challenge revealed a blunted myocardial inotropic response in wild type diabetic animals, Txnip-CKO diabetic mice retained a greater cardiac response to β-adrenergic stimulation. An ex vivo analysis of perfused hearts further demonstrated that the enhanced functional reserve afforded by deletion of Txnip was associated with myocardial glucose utilization during β-adrenergic stimulation. Thus, a high extracellular glucose concentration represses glucose uptake into the cytoplasm via Txnip-mediated inhibition of GLUTs. The metabolic alterations affected by Txnip deletion promote myocardial glucose uptake, directing cardiomyocyte towards enhanced functional reserve under diabetic conditions. These results provide a novel link between GLUTs and Txnip and highlight a fundamental regulatory mechanism of glucose homeostasis in the heart.

scholarly journals Thioredoxin-interacting protein regulates glucose metabolism and improves the intracellular redox state in bovine oocytes during in vitro maturation

2020 ◽  
Vol 318 (3) ◽  
pp. E405-E416
Author(s):  
XiaoLong Jiang ◽  
YunWei Pang ◽  
ShanJiang Zhao ◽  
HaiSheng Hao ◽  
XueMing Zhao ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Oocyte Maturation ◽  
In Vitro Maturation ◽  
Mrna Levels ◽  
Interacting Protein ◽  
Thioredoxin Interacting Protein ◽  
Glut1 Expression ◽  
Bovine Oocytes

The extent of glucose metabolism during oocyte maturation is closely related to oocyte developmental potential. Thioredoxin-interacting protein (TXNIP) is an α-arrestin family protein that negatively regulates glucose uptake into cells. However, little information is available regarding the function of TXNIP in bovine oocytes. Accordingly, the present study was performed to investigate the influence of TXNIP on glucose metabolism in bovine oocytes during in vitro maturation. Pharmacological inhibition of TXNIP by azaserine enhanced glucose uptake and imparted a specific metabolic effect on glycolysis and pentose phosphate pathway (PPP). RNA interference (RNAi) was adopted to further determine the biological significance of TXNIP in regulating glucose metabolism. The maturation rate and the developmental competence of TXNIP siRNA-treated oocytes were significantly improved. Knockdown of TXNIP in bovine oocytes significantly increased glycolysis by increasing the activities of phosphofructokinase (PFK), pyruvate kinase, and lactate dehydrogenase; pyruvate and lactate production; and intracellular ATP level, as well as mitochondrial activity. Furthermore, glucose metabolism through PPP was also enhanced by TXNIP depletion, as TXNIP siRNA treatment promoted glucose-6-phosphate dehydrogenase (G6PDH) activity and NADPH content, and helped maintain a high level of glutathione and a low level of reactive oxygen species within the oocytes. Further studies revealed that inhibition of TXNIP resulted increases in glucose transporter 1 (GLUT1) expression, as well as PFK1 platelet isoform ( PFKP) and G6PDH mRNA levels. These results reveal that TXNIP depletion promotes oocyte maturation by enhancing both glycolysis and the PPP. During in vitro maturation of bovine oocytes, TXNIP serves as a key regulator of glucose uptake by controlling GLUT1 expression.

Neural control of glucose uptake by skeletal muscle after central administration of NMDA

1995 ◽  
Vol 268 (2) ◽  
pp. R492-R497 ◽  
Author(s):  
C. H. Lang ◽  
M. Ajmal ◽  
A. G. Baillie
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Glucose Uptake ◽  
Neural Control ◽  
Plasma Insulin ◽  
Regional Blood Flow ◽  
Muscle Blood Flow ◽  
Whole Body ◽  
Glucose Disposal ◽  
Central Administration

Intracerebroventricular injection of N-methyl-D-aspartate (NMDA) produces hyperglycemia and increases whole body glucose uptake. The purpose of the present study was to determine in rats which tissues are responsible for the elevated rate of glucose disposal. NMDA was injected intracerebroventricularly, and the glucose metabolic rate (Rg) was determined for individual tissues 20-60 min later using 2-deoxy-D-[U-14C]glucose. NMDA decreased Rg in skin, ileum, lung, and liver (30-35%) compared with time-matched control animals. In contrast, Rg in skeletal muscle and heart was increased 150-160%. This increased Rg was not due to an elevation in plasma insulin concentrations. In subsequent studies, the sciatic nerve in one leg was cut 4 h before injection of NMDA. NMDA increased Rg in the gastrocnemius (149%) and soleus (220%) in the innervated leg. However, Rg was not increased after NMDA in contralateral muscles from the denervated limb. Data from a third series of experiments indicated that the NMDA-induced increase in Rg by innervated muscle and its abolition in the denervated muscle were not due to changes in muscle blood flow. The results of the present study indicate that 1) central administration of NMDA increases whole body glucose uptake by preferentially stimulating glucose uptake by skeletal muscle, and 2) the enhanced glucose uptake by muscle is neurally mediated and independent of changes in either the plasma insulin concentration or regional blood flow.

scholarly journals AS160 Regulates Insulin- and Contraction-stimulated Glucose Uptake in Mouse Skeletal Muscle*

2006 ◽  
Vol 281 (42) ◽  
pp. 31478-31485
Author(s):  
Henning F. Kramer ◽  
Carol A. Witczak ◽  
Eric B. Taylor ◽  
Nobuharu Fujii ◽  
Michael F. Hirshman ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Mouse Skeletal Muscle
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