Exercise-Induced Hyperinsulinism: A Failure of Monocarboxylate Transporter 1 Expression Silencing

2012 ◽  
pp. 172-181 ◽  
Author(s):  
Timo Otonkoski ◽  
Thomas Meissner
Keyword(s):  
Monocarboxylate Transporter ◽  
Monocarboxylate Transporter 1 ◽  
Exercise Induced

Training does not protect against exhaustive exercise-induced lactate transport capacity alterations

2000 ◽  
Vol 278 (6) ◽  
pp. E1045-E1052 ◽  
Author(s):  
Nicolas Eydoux ◽  
Guillaume Py ◽  
Karen Lambert ◽  
Hervé Dubouchaud ◽  
Christian Préfaut ◽  
...  
Keyword(s):  
Endurance Training ◽  
Exhaustive Exercise ◽  
Monocarboxylate Transporter ◽  
Transport Capacity ◽  
Lactate Transport ◽  
Monocarboxylate Transporter 1 ◽  
Saturation Properties ◽  
Apparent Loss ◽  
Male Wistar Rats ◽  
Exercise Induced

The effects of endurance training on lactate transport capacity remain controversial. This study examined whether endurance training 1) alters lactate transport capacity, 2) can protect against exhaustive exercise-induced lactate transport alteration, and 3) can modify heart and oxidative muscle monocarboxylate transporter 1 (MCT1) content. Forty male Wistar rats were divided into control (C), trained (T), exhaustively exercised (E), and trained and exercised (TE) groups. Rats in the T and TE groups ran on a treadmill (1 h/day, 5 days/wk at 25 m/min, 10% incline) for 5 wk; C and E were familiarized with the exercise task for 5 min/day. Before being killed, E and TE rats underwent exhaustive exercise (25 m/min, 10% grade), which lasted 80 and 204 min, respectively ( P < 0.05). Although lactate transport measurements (zero- trans) did not differ between groups C and T, both E and TE groups presented an apparent loss of protein saturation properties. In the trained groups, MCT1 content increased in soleus (+28% for T and +26% for TE; P < 0.05) and heart muscle (+36% for T and +33% for TE; P < 0.05). Moreover, despite the metabolic adaptations typically observed after endurance training, we also noted increased lipid peroxidation byproducts after exhaustive exercise. We concluded that 1) endurance training does not alter lactate transport capacity, 2) exhaustive exercise-induced lactate transport alteration is not prevented by training despite increased MCT1 content, and 3) exercise-induced oxidative stress may enhance the passive diffusion responsible for the apparent loss of saturation properties, possibly masking lactate transport regulation.

scholarly journals Physical Exercise–Induced Hypoglycemia Caused by Failed Silencing of Monocarboxylate Transporter 1 in Pancreatic β Cells

2007 ◽  
Vol 81 (3) ◽  
pp. 467-474 ◽  
Author(s):  
Timo Otonkoski ◽  
Hong Jiao ◽  
Nina Kaminen-Ahola ◽  
Isabel Tapia-Paez ◽  
Mohammed S. Ullah ◽  
...  
Keyword(s):  
Physical Exercise ◽  
Monocarboxylate Transporter ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Monocarboxylate Transporter 1 ◽  
Exercise Induced

scholarly journals Does exercise-induced hypoxemia modify lactate influx into erythrocytes and hemorheological parameters in athletes?

2004 ◽  
Vol 97 (3) ◽  
pp. 1053-1058 ◽  
Author(s):  
Philippe Connes ◽  
Didier Bouix ◽  
Guillaume Py ◽  
Corinne Caillaud ◽  
Pascale Kippelen ◽  
...  
Keyword(s):  
Blood Cells ◽  
Aerobic Power ◽  
Venous Blood ◽  
Maximal Aerobic Power ◽  
Monocarboxylate Transporter ◽  
Arterial Oxygen ◽  
Plasma Lactate ◽  
Monocarboxylate Transporter 1 ◽  
Arterial Oxygen Partial Pressure ◽  
Exercise Induced

This study investigated 1) red blood cells (RBC) rigidity and 2) lactate influxes into RBCs in endurance-trained athletes with and without exercise-induced hypoxemia (EIH). Nine EIH and six non-EIH subjects performed a submaximal steady-state exercise on a cyclo-ergometer at 60% of maximal aerobic power for 10 min, followed by 15 min at 85% of maximal aerobic power. At rest and at the end of exercise, arterialized blood was sampled for analysis of arterialized pressure in oxygen, and venous blood was drawn for analysis of plasma lactate concentrations and hemorheological parameters. Lactate influxes into RBCs were measured at three labeled [U-14C]lactate concentrations (1.6, 8.1, and 41 mM) on venous blood sampled at rest. The EIH subjects had higher maximal oxygen uptake than non-EIH ( P < 0.05). Total lactate influx was significantly higher in RBCs from EIH compared with non-EIH subjects at 8.1 mM (1,498.1 ± 87.8 vs. 1,035.9 ± 114.8 nmol·ml−1·min−1; P < 0.05) and 41 mM (2,562.0 ± 145.0 vs. 1,618.1 ± 149.4 nmol·ml−1·min−1; P < 0.01). Monocarboxylate transporter-1-mediated lactate influx was also higher in EIH at 8.1 mM ( P < 0.05) and 41 mM ( P < 0.01). The drop in arterial oxygen partial pressure was negatively correlated with total lactate influx measured at 8.1 mM ( r = −0.82, P < 0.05) and 41 mM ( r = −0.84, P < 0.05) in the two groups together. Plasma lactate concentrations and hemorheological data were similar in the two groups at rest and at the end of exercise. The results showed higher monocarboxylate transporter-1-mediated lactate influx in the EIH subjects and suggested that EIH could modify lactate influx into erythrocyte. However, higher lactate influx in EIH subjects was not accompanied by an increase in RBC rigidity.

Treatment of Lymphoid and Myeloid Malignancies by Immunomodulatory Drugs

2019 ◽  
Vol 19 (1) ◽  
pp. 51-78 ◽  
Author(s):  
Ota Fuchs
Keyword(s):  
Clinical Trials ◽  
Transcription Factors ◽  
Ubiquitin Ligase ◽  
Mononuclear Cells ◽  
E3 Ubiquitin Ligase ◽  
Lymphocytic Leukemia ◽  
Monocarboxylate Transporter ◽  
Immunomodulatory Drugs ◽  
Monocarboxylate Transporter 1 ◽  
Argonaute 2

Thalidomide and its derivatives (lenalidomide, pomalidomide, avadomide, iberdomide hydrochoride, CC-885 and CC-90009) form the family of immunomodulatory drugs (IMiDs). Lenalidomide (CC5013, Revlimid®) was approved by the US FDA and the EMA for the treatment of multiple myeloma (MM) patients, low or intermediate-1 risk transfusion-dependent myelodysplastic syndrome (MDS) with chromosome 5q deletion [del(5q)] and relapsed and/or refractory mantle cell lymphoma following bortezomib. Lenalidomide has also been studied in clinical trials and has shown promising activity in chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL). Lenalidomide has anti-inflammatory effects and inhibits angiogenesis. Pomalidomide (CC4047, Imnovid® [EU], Pomalyst® [USA]) was approved for advanced MM insensitive to bortezomib and lenalidomide. Other IMiDs are in phases 1 and 2 of clinical trials. Cereblon (CRBN) seems to have an important role in IMiDs action in both lymphoid and myeloid hematological malignancies. Cereblon acts as the substrate receptor of a cullin-4 really interesting new gene (RING) E3 ubiquitin ligase CRL4CRBN. This E3 ubiquitin ligase in the absence of lenalidomide ubiquitinates CRBN itself and the other components of CRL4CRBN complex. Presence of lenalidomide changes specificity of CRL4CRBN which ubiquitinates two transcription factors, IKZF1 (Ikaros) and IKZF3 (Aiolos), and casein kinase 1α (CK1α) and marks them for degradation in proteasomes. Both these transcription factors (IKZF1 and IKZF3) stimulate proliferation of MM cells and inhibit T cells. Low CRBN level was connected with insensitivity of MM cells to lenalidomide. Lenalidomide decreases expression of protein argonaute-2, which binds to cereblon. Argonaute-2 seems to be an important drug target against IMiDs resistance in MM cells. Lenalidomide decreases also basigin and monocarboxylate transporter 1 in MM cells. MM cells with low expression of Ikaros, Aiolos and basigin are more sensitive to lenalidomide treatment. The CK1α gene (CSNK1A1) is located on 5q32 in commonly deleted region (CDR) in del(5q) MDS. Inhibition of CK1α sensitizes del(5q) MDS cells to lenalidomide. CK1α mediates also survival of malignant plasma cells in MM. Though, inhibition of CK1α is a potential novel therapy not only in del(5q) MDS but also in MM. High level of full length CRBN mRNA in mononuclear cells of bone marrow and of peripheral blood seems to be necessary for successful therapy of del(5q) MDS with lenalidomide. While transfusion independence (TI) after lenalidomide treatment is more than 60% in MDS patients with del(5q), only 25% TI and substantially shorter duration of response with occurrence of neutropenia and thrombocytopenia were achieved in lower risk MDS patients with normal karyotype treated with lenalidomide. Shortage of the biomarkers for lenalidomide response in these MDS patients is the main problem up to now.

scholarly journals Monocarboxylate transporter-1 (MCT1) protein expression in head and neck cancer affects clinical outcome

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Martin Leu ◽  
J. Kitz ◽  
Y. Pilavakis ◽  
S. Hakroush ◽  
H. A. Wolff ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Protein Expression ◽  
Head And Neck ◽  
Cox Regression ◽  
Locally Advanced ◽  
Monocarboxylate Transporter ◽  
Positive Staining ◽  
Monocarboxylate Transporter 1 ◽  
Prognostic Features ◽  
Hpv Status

AbstractTreatment of locally advanced, unresectable head and neck squamous cell carcinoma (HNSCC) often yields only modest results with radiochemotherapy (RCT) as standard of care. Prognostic features related to outcome upon RCT might be highly valuable to improve treatment. Monocarboxylate transporters-1 and -4 (MCT1/MCT4) were evaluated as potential biomarkers. A cohort of HNSCC patients without signs for distant metastases was assessed eliciting 82 individuals eligible whereof 90% were diagnosed with locally advanced stage IV. Tumor specimens were stained for MCT1 and MCT4 in the cell membrane by immunohistochemistry. Obtained data were evaluated with respect to overall (OS) and progression-free survival (PFS). Protein expression of MCT1 and MCT4 in cell membrane was detected in 16% and 85% of the tumors, respectively. Expression of both transporters was not statistically different according to the human papilloma virus (HPV) status. Positive staining for MCT1 (n = 13, negative in n = 69) strongly worsened PFS with a hazard ratio (HR) of 3.1 (95%-confidence interval 1.6–5.7, p < 0.001). OS was likewise affected with a HR of 3.8 (2.0–7.3, p < 0.001). Multivariable Cox regression confirmed these findings. We propose MCT1 as a promising biomarker in HNSCC treated by primary RCT.

scholarly journals Synthesis and radiofluorination of [18F]F-BAY-8002: a novel potential radiotracer for PET imaging of monocarboxylate transporter 1

2021 ◽  
Vol 96-97 ◽  
pp. S74-S75
Author(s):  
Masoud Sadeghzadeh ◽  
Barbara Wenzel ◽  
Friedrich-Alexander Ludwig ◽  
Klaus Kopka ◽  
Rares Moldovan ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Monocarboxylate Transporter ◽  
Monocarboxylate Transporter 1

scholarly journals Monocarboxylate transporter 1 blockade with AZD3965 inhibits lipid biosynthesis and increases tumour immune cell infiltration

2020 ◽  
Vol 122 (6) ◽  
pp. 895-903 ◽  
Author(s):  
Mounia Beloueche-Babari ◽  
Teresa Casals Galobart ◽  
Teresa Delgado-Goni ◽  
Slawomir Wantuch ◽  
Harold G. Parkes ◽  
...  
Keyword(s):  
Immune Cell ◽  
Lipid Biosynthesis ◽  
Monocarboxylate Transporter ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Monocarboxylate Transporter 1

Monocarboxylate transporter 1 is up-regulated in Caco-2 cells by the methionine precursor DL-2-hydroxy-(4-methylthio)butanoic acid

2014 ◽  
Vol 202 (3) ◽  
pp. 555-560 ◽  
Author(s):  
Raquel Martín-Venegas ◽  
M.Teresa Brufau ◽  
Oriol Mañas-Cano ◽  
Yves Mercier ◽  
Magalie K. Nonis ◽  
...  
Keyword(s):  
Monocarboxylate Transporter ◽  
Butanoic Acid ◽  
Monocarboxylate Transporter 1

scholarly journals Comparison of Lactate Transport in Astroglial Cells and Monocarboxylate Transporter 1 (MCT 1) ExpressingXenopus laevisOocytes

1997 ◽  
Vol 272 (48) ◽  
pp. 30096-30102 ◽  
Author(s):  
Stefan Bröer ◽  
Basim Rahman ◽  
Gioranni Pellegri ◽  
Luc Pellerin ◽  
Jean-Luc Martin ◽  
...  
Keyword(s):  
Monocarboxylate Transporter ◽  
Lactate Transport ◽  
Astroglial Cells ◽  
Monocarboxylate Transporter 1
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