Giant Oyster Mushroom Pleurotus giganteus (Agaricomycetes) Enhances Adipocyte Differentiation and Glucose Uptake via Activation of PPARγ and Glucose Transporters 1 and 4 in 3T3-L1 Cells

Cells- and organisms-on-a-chip strategies were used to highlight the role of the molecular motor dynamin in regulating the translocation of specific glucose transporters.

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Expression of Glucose Transporters 1 and 3 in Metastatic and Non-Metastatic Lower Lip Squamous Cell Carcinoma

Brazilian Dental Journal ◽

10.1590/0103-6440201300054 ◽

2014 ◽

Vol 25 (5) ◽

pp. 372-378 ◽

Cited By ~ 4

Author(s):

Clarissa Favero Demeda ◽

Cyntia Helena Pereira de Carvalho ◽

Ana Rafaela Luz de Aquino ◽

Cassiano Francisco Weege Nonaka ◽

Lélia Batista de Souza ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Glucose Uptake ◽

Squamous Cell ◽

Histological Grade ◽

Glucose Transporters ◽

Nodal Metastasis ◽

Invasive Front ◽

Lower Lip ◽

Glut 1

This study aimed to evaluate the immunoexpression of glucose transporters 1 (GLUT-1) and 3 (GLUT-3) in metastatic and non-metastatic lower lip squamous cell carcinoma (LLSCC). Twenty LLSCCs with regional nodal metastasis and 20 LLSCCs without metastasis were selected. The distribution of staining and the percentage of GLUT-1 and GLUT-3 staining in each tumor core and at the deep invasive front were assessed. Most tumors (70%) exhibited peripheral staining for GLUT-1 in nests, sheets and islands of neoplastic cells, whereas predominantly central staining was observed for GLUT-3 (72.5%). A high percentage of GLUT-1-positive cells was observed at the deep invasive front and in the tumor core of metastatic and non-metastatic tumors (p>0.05). The percentage of GLUT-1-positive cells was much higher than that of GLUT-3-positive cells both in the deep invasive front (p<0.001) and in the tumor core (p<0.001) of LLSCCs. No significant differences in the percentage of GLUT-1- and GLUT-3-positive cells were observed according to nodal metastasis, clinical stage or histological grade of malignancy (p>0.05). In conclusion, the results of the present study suggest an important role of GLUT-1 in glucose uptake in LLSCCs, although this protein does not seem to be involved in the progression of these tumors. On the other hand, GLUT-3 expression may represent a secondary glucose uptake mechanism in LLSCCs.

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Functional expression of sodium-glucose transporters in cancer

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1511698112 ◽

2015 ◽

Vol 112 (30) ◽

pp. E4111-E4119 ◽

Cited By ~ 100

Author(s):

Claudio Scafoglio ◽

Bruce A. Hirayama ◽

Vladimir Kepe ◽

Jie Liu ◽

Chiara Ghezzi ◽

...

Keyword(s):

Cell Survival ◽

Glucose Uptake ◽

Cancer Cell ◽

Pet Imaging ◽

Xenograft Model ◽

Glucose Transporters ◽

Functional Expression ◽

Sglt2 Inhibitors ◽

Cancer Cell Survival

Glucose is a major metabolic substrate required for cancer cell survival and growth. It is mainly imported into cells by facilitated glucose transporters (GLUTs). Here we demonstrate the importance of another glucose import system, the sodium-dependent glucose transporters (SGLTs), in pancreatic and prostate adenocarcinomas, and investigate their role in cancer cell survival. Three experimental approaches were used: (i) immunohistochemical mapping of SGLT1 and SGLT2 distribution in tumors; (ii) measurement of glucose uptake in fresh isolated tumors using an SGLT-specific radioactive glucose analog, α-methyl-4-deoxy-4-[18F]fluoro-d-glucopyranoside (Me4FDG), which is not transported by GLUTs; and (iii) measurement of in vivo SGLT activity in mouse models of pancreatic and prostate cancer using Me4FDG-PET imaging. We found that SGLT2 is functionally expressed in pancreatic and prostate adenocarcinomas, and provide evidence that SGLT2 inhibitors block glucose uptake and reduce tumor growth and survival in a xenograft model of pancreatic cancer. We suggest that Me4FDG-PET imaging may be used to diagnose and stage pancreatic and prostate cancers, and that SGLT2 inhibitors, currently in use for treating diabetes, may be useful for cancer therapy.

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AMPK-Mediated Regulation of Alpha-Arrestins and Protein Trafficking

International Journal of Molecular Sciences ◽

10.3390/ijms20030515 ◽

2019 ◽

Vol 20 (3) ◽

pp. 515 ◽

Cited By ~ 11

Author(s):

Allyson F. O’Donnell ◽

Martin C. Schmidt

Keyword(s):

Glucose Uptake ◽

Protein Trafficking ◽

Transmembrane Domain ◽

Carbon Sources ◽

Cellular Metabolism ◽

Glucose Transporters ◽

Adenosine Monophosphate ◽

Kinetic Properties ◽

Glucose Limitation ◽

Additional Layer

Abstract: The adenosine monophosphate-activated protein kinase (AMPK) plays a central role in the regulation of cellular metabolism. Recent studies reveal a novel role for AMPK in the regulation of glucose and other carbohydrates flux by controlling the endocytosis of transporters. The first step in glucose metabolism is glucose uptake, a process mediated by members of the GLUT/SLC2A (glucose transporters) or HXT (hexose transporters) family of twelve-transmembrane domain glucose transporters in mammals and yeast, respectively. These proteins are conserved from yeast to humans, and multiple transporters—each with distinct kinetic properties—compete for plasma membrane occupancy in order to enhance or limit the rate of glucose uptake. During growth in the presence of alternative carbon sources, glucose transporters are removed and replaced with the appropriate transporter to help support growth in response to this environment. New insights into the regulated protein trafficking of these transporters reveal the requirement for specific α-arrestins, a little-studied class of protein trafficking adaptor. A defining feature of the α-arrestins is that each contains PY-motifs, which can bind to the ubiquitin ligases from the NEDD4/Rsp5 (Neural precursor cell Expressed, Developmentally Down-regulated 4 and Reverses Spt- Phenotype 5, respectively) family. Specific association of α-arrestins with glucose and carbohydrate transporters is thought to bring the ubiquitin ligase in close proximity to its membrane substrate, and thereby allows the membrane cargo to become ubiquitinated. This ubiquitination in turn serves as a mark to stimulate endocytosis. Recent results show that AMPK phosphorylation of the α-arrestins impacts their abundance and/or ability to stimulate carbohydrate transporter endocytosis. Indeed, AMPK or glucose limitation also controls α-arrestin gene expression, adding an additional layer of complexity to this regulation. Here, we review the recent studies that have expanded the role of AMPK in cellular metabolism to include regulation of α-arrestin-mediated trafficking of transporters and show that this mechanism of regulation is conserved over the ~150 million years of evolution that separate yeast from man.

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Functional Expression of Sodium-Dependent Glucose Transporter in Amelogenesis

Journal of Dental Research ◽

10.1177/0022034520916130 ◽

2020 ◽

Vol 99 (8) ◽

pp. 977-986

Author(s):

H. Ida-Yonemochi ◽

K. Otsu ◽

H. Harada ◽

H. Ohshima

Keyword(s):

Organ Culture ◽

Glucose Uptake ◽

Glucose Transport ◽

Glucose Transporter ◽

Glucose Transporters ◽

Maturation Stage ◽

Sodium Dependent ◽

Tooth Morphogenesis

Glucose is an essential source of energy for mammalian cells and is transported into the cells by glucose transporters. There are 2 types of glucose transporters: one is a passive glucose transporter, GLUT ( SLC2A), and the other is a sodium-dependent active glucose transporter, SGLT ( SLC5A). We previously reported that the expression of GLUTs during tooth development is precisely and spatiotemporally controlled and that the glucose uptake mediated by GLUT1 plays a crucial role in early tooth morphogenesis and tooth size determination. This study aimed to clarify the localization and roles of SGLT1 and SGLT2 in murine ameloblast differentiation by using immunohistochemistry, immunoelectron microscopy, an in vitro tooth organ culture experiment, and in vivo administration of an inhibitor of SGLT1/2, phloridzin. SGLT1, which has high affinity with glucose, was immunolocalized in the early secretory ameloblasts and the ruffle-ended ameloblasts in the maturation stage. However, SGLT2, which has high glucose transport capacity, was observed in the stratum intermedium, papillary layer, and ameloblasts at the maturation stage and colocalized with Na+-K+-ATPase. The inhibition of SGLT1/2 by phloridzin in the tooth germs induced the disturbance of ameloblast differentiation and enamel matrix formation both in vitro (organ culture) and in vivo (mouse model). The expression of SGLT1 and SGLT2 was significantly upregulated in hypoxic conditions in the ameloblast-lineage cells. These findings suggest that the active glucose uptake mediated by SGLT1 and SGLT2 is strictly regulated and dependent on the intra- and extracellular microenvironments during tooth morphogenesis and that the appropriate passive and active glucose transport is an essential event in amelogenesis.

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