Because of the unobvious early symptoms and low 5-year survival rate, the early diagnosis and treatment is of great significance for patients with non-small cell lung cancer. Glucose transporter-1 is the most widely distributed glucose transporters in various tissue cells in the human body, whose expression in non-small cell lung cancer is closely related to the histological types, lymph node metastasis, degree of differentiation, progression and prognosis.
Carcinoma, Non-Small-Cell Lung/diagnostic imaging* ; Fluorodeoxyglucose F18 ; Glucose Transport Proteins, Facilitative ; Glucose Transporter Type 1 ; Humans ; Lung Neoplasms/diagnostic imaging* ; Positron Emission Tomography Computed Tomography ; Positron-Emission Tomography ; Radiopharmaceuticals

Facilitative glucose transporters (GLUT) are proteins that mediate glucose transmembrane transport in the form of facilitated diffusion, which play an important role in regulating cell energy metabolism. There are many breakthroughs in researches of facilitative GLUT in recent years. It has been known that there are 14 subtypes of facilitative GLUT with obvious tissue specificity in distribution and physiological function. In the present review, the tissue and cellular distribution, subcellular localization, expression regulation, physiological function and the relationship to diseases of facilitative GLUT subtypes were summarized, in order to further understand their physiological and pathophysiological significances.
Biological Transport ; Disease ; Energy Metabolism ; Glucose ; Glucose Transport Proteins, Facilitative ; physiology ; Humans

Rapidly involuting congenital hemangioma (RICH), a subtype of congenital hemangioma (CH), is fully developed at birth and undergoes rapid involution by 6–14 months of age. Clinically, this vascular lesion differs from both non-involuting CH and infantile hemangiomas. It is important to distinguish between this rare condition and other vascular lesions to ensure appropriate management (active intervention vs. non-intervention). We describe 5 patients diagnosed with RICH based on clinicopathological and/or imaging studies. Three patients showed red-stippled bluish to purplish tense plaques and two showed slightly depressed red-stippled hypopigmented rubbery patches at their initial visit. Spontaneous involution commenced shortly after birth, and complete involution occurred by 16.0±9.9 months of age. Doppler ultrasonography and magnetic resonance imaging were performed for further evaluation. Histopathological examination revealed vascular lobules of various sizes without true arteriovenous microfistulae, and thickened intra- and interlobular vessels were prominent with glucose transporter isoform-1 protein negativity.
Glucose Transport Proteins, Facilitative ; Hemangioma ; Humans ; Magnetic Resonance Imaging ; Parturition ; Transcutaneous Electric Nerve Stimulation ; Ultrasonography, Doppler

BACKGROUND: Diabetic nephropathy (DN) is the most serious microvascular complication of diabetes mellitus and is one of the leading causes of end stage renal failure. In previous studies, the contribution of genetic susceptibility to DN showed inconsistent results. In this study, we investigated the association between the solute carrier family 2 facilitated glucose transporter member 1 (SLC2A1) HaeIII polymorphism and DN in Korean patients with type 2 diabetes mellitus (T2DM) according to disease duration. METHODS: A total of 846 patients with T2DM (mean age, 61.3 ± 12.3 years; mean duration of T2DM, 10.3 ± 7.9 years; 55.3% men) who visited the Chungbuk National University Hospital were investigated. The HaeIII polymorphism of the SLC2A1 gene was determined by the real time polymerase chain reaction method. Genotyping results were presented as GG, AG, or AA. A subgroup analysis was performed according to duration of T2DM (≤ 10 years, < 10 years). RESULTS: The AG + AA genotype showed a significantly higher risk of DN compared with the GG genotype in patients with a type 2 DM duration less than 10 years (12.4% vs. 4.2%; P < 0.001). No significant differences were observed in terms of other diabetic complications, including retinopathy, peripheral neuropathy, cardiovascular disease, cerebrovascular disease or peripheral artery disease, according to the genotypes of the SLC2A1 HaeIII polymorphism. CONCLUSION: The SLC2A1 HaeIII polymorphism was associated with DN in Korean patients with T2DM, particularly in the group with a relatively short disease duration.
Cardiovascular Diseases ; Cerebrovascular Disorders ; Chungcheongbuk-do ; Diabetes Complications ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Diabetic Nephropathies ; Genetic Predisposition to Disease ; Genotype ; Glucose Transport Proteins, Facilitative ; Humans ; Methods ; Peripheral Arterial Disease ; Peripheral Nervous System Diseases ; Polymorphism, Single Nucleotide ; Real-Time Polymerase Chain Reaction ; Renal Insufficiency

PURPOSE: The present study investigated the dynamics and prognostic role of messenger RNA (mRNA) expression responsible for 18F-fluorodeoxyglucose (FDG) uptake in FDG positron emission tomography (PET) and radioactive iodine (131I) uptake in whole-body radioactive iodine scans (WBS) in papillary thyroid cancer (PTC) patients. MATERIALS AND METHODS: The primary and processed data were downloaded from the Genomic Data Commons Data Portal. Expression data for sodium/iodide symporter (solute carrier family 5 member 5, SLC5A5), hexokinase (HK1–3), glucose-6-phosphate dehydrogenase (G6PD), and glucose transporter (solute carrier family 2, SLC2A1–4) mRNA were collected. RESULTS: Expression of SLC5A5 mRNA were negatively correlated with SLC2A1 mRNA and positively correlated with SLC2A4 mRNA. In PTC with BRAF mutations, expressions of SLC2A1, SLC2A3, HK2, and HK3 mRNA were higher than those in PTC without BRAF mutations. Expression of SLC5A5, SLC2A4, HK1, and G6PD mRNA was lower in PTC without BRAF mutation. PTCs with higher expression of SLC5A5 mRNA had more favorable disease-free survival, but no association with overall survival. CONCLUSION: Expression of SLC5A5 mRNA was negatively correlated with SLC2A1 mRNA. This finding provides a molecular basis for the management of PTC with negative WBS using 18F-FDG PET scans. In addition, higher expression of SLC5A5 mRNA was associated with less PTC recurrence, but not with deaths.
Disease-Free Survival ; Fluorodeoxyglucose F18 ; Genome* ; Glucose Transport Proteins, Facilitative ; Glucosephosphate Dehydrogenase ; Hexokinase ; Humans ; Iodine ; Ion Transport ; Positron-Emission Tomography ; Recurrence ; RNA, Messenger* ; Thyroid Gland* ; Thyroid Neoplasms*

BACKGROUND: The nuclear receptor peroxisome proliferator-activator gamma (PPARγ) is a useful therapeutic target for obesity and diabetes, but its role in protecting β-cell function and viability is unclear. METHODS: To identify the potential functions of PPARγ in β-cells, we treated mouse insulinoma 6 (MIN6) cells with the PPARγ agonist pioglitazone in conditions of lipotoxicity, endoplasmic reticulum (ER) stress, and inflammation. RESULTS: Palmitate-treated cells incubated with pioglitazone exhibited significant improvements in glucose-stimulated insulin secretion and the repression of apoptosis, as shown by decreased caspase-3 cleavage and poly (adenosine diphosphate [ADP]-ribose) polymerase activity. Pioglitazone also reversed the palmitate-induced expression of inflammatory cytokines (tumor necrosis factor α, interleukin 6 [IL-6], and IL-1β) and ER stress markers (phosphor-eukaryotic translation initiation factor 2α, glucose-regulated protein 78 [GRP78], cleaved-activating transcription factor 6 [ATF6], and C/EBP homologous protein [CHOP]), and pioglitazone significantly attenuated inflammation and ER stress in lipopolysaccharide- or tunicamycin-treated MIN6 cells. The protective effect of pioglitazone was also tested in pancreatic islets from high-fat-fed KK-Ay mice administered 0.02% (wt/wt) pioglitazone or vehicle for 6 weeks. Pioglitazone remarkably reduced the expression of ATF6α, GRP78, and monocyte chemoattractant protein-1, prevented α-cell infiltration into the pancreatic islets, and upregulated glucose transporter 2 (Glut2) expression in β-cells. Moreover, the preservation of β-cells by pioglitazone was accompanied by a significant reduction of blood glucose levels. CONCLUSION: Altogether, these results support the proposal that PPARγ agonists not only suppress insulin resistance, but also prevent β-cell impairment via protection against ER stress and inflammation. The activation of PPARγ might be a new therapeutic approach for improving β-cell survival and insulin secretion in patients with diabetes mellitus
Animals ; Apoptosis ; Blood Glucose ; Caspase 3 ; Chemokine CCL2 ; Cytokines ; Diabetes Mellitus ; Endoplasmic Reticulum Stress* ; Endoplasmic Reticulum* ; Glucose Transport Proteins, Facilitative ; Humans ; Inflammation* ; Insulin ; Insulin Resistance ; Insulin-Secreting Cells ; Insulinoma ; Interleukin-6 ; Islets of Langerhans ; Mice ; Necrosis ; Obesity ; Peptide Initiation Factors ; Peroxisomes ; Repression, Psychology ; Transcription Factors

In the present study, we compared the cell-specific expression and changes protein levels in the glucose transporters (GLUTs) 1 and 3, the major GLUTs in the mouse and gerbil brains using immunohistochemistry and Western blot analysis. In both mouse and gerbils, GLUT1 immunoreactivity was mainly found in the blood vessels in the dentate gyrus, while GLUT3 immunoreactivity was detected in the subgranular zone and the molecular layer of the dentate gyrus. GLUT1-immunoreactivity in blood vessels and GLUT1 protein levels were significantly decreased with age in the mice and gerbils, respectively. In addition, few GLUT3-immunoreactive cells were found in the subgranular zone in aged mice and gerbils, but GLUT3-immunoreactivity was abundantly found in the polymorphic layer of dentate gyrus in mice and gerbils with a dot-like pattern. Based on the double immunofluorescence study, GLUT3-immunoreactive structures in gerbils were localized in the glial fibrillary acidic protein-immunoreactive astrocytes in the dentate gyrus. Western blot analysis showed that GLUT3 expression in the hippocampal homogenates was slightly, although not significantly, decreased with age in mice and gerbils, respectively. These results indicate that the reduction in GLUT1 in the blood vessels of dentate gyrus and GLUT3 in the subgranular zone of dentate gyrus may be associated with the decrease in uptake of glucose into brain and neuroblasts in the dentate gyrus. In addition, the expression of GLUT3 in the astrocytes in polymorphic layer of dentate gyrus may be associated with metabolic changes in glucose in aged hippocampus.
Aging* ; Animals ; Astrocytes ; Blood Vessels ; Blotting, Western ; Brain ; Dentate Gyrus* ; Fluorescent Antibody Technique ; Gerbillinae* ; Glucose Transport Proteins, Facilitative* ; Glucose Transporter Type 1 ; Glucose* ; Hippocampus ; Immunohistochemistry ; Mice*

PURPOSE: To characterize the relationship between serum estradiol levels and the expression of glucose transporter type 4 (Glut4) in the pubococcygeus and iliococcygeus muscles in female rats. METHODS: The muscles were excised from virgin rats during the metestrus and proestrus stages of the estrous cycle, and from sham and ovariectomized rats implanted with empty or estradiol benzoate–filled capsules. The expression of estrogen receptors (ERs) was inspected in the muscles at metestrus and proestrus. Relative Glut4 expression, glycogen content, and serum glucose levels were measured. Appropriate statistical tests were done to identify significant differences (P≤0.05). RESULTS: The pubococcygeus and iliococcygeus muscles expressed ERα and ERβ. Glut4 expression and glycogen content in the pubococcygeus muscle were higher at proestrus than at metestrus. No significant changes were observed in the iliococcygeus muscle. In ovariectomized rats, the administration of estradiol benzoate increased Glut4 expression and glycogen content in the pubococcygeus muscle alone. CONCLUSIONS: High serum estradiol levels increased Glut4 expression and glycogen content in the pubococcygeus muscle, but not in the iliococcygeus muscle.
Animals ; Benzoates ; Blood Glucose ; Capsules ; Estradiol* ; Estrous Cycle ; Female ; Glucose Transport Proteins, Facilitative* ; Glucose Transporter Type 4* ; Glucose* ; Glycogen ; Humans ; Metabolism ; Metestrus ; Muscles* ; Ovariectomy ; Pelvic Floor* ; Proestrus ; Rats* ; Receptors, Estrogen

My professional journey to understand the glucose homeostasis began in the 1990s, starting from cloning of the promoter region of glucose transporter type 2 (GLUT2) gene that led us to establish research foundation of my group. When I was a graduate student, I simply thought that hyperglycemia, a typical clinical manifestation of type 2 diabetes mellitus (T2DM), could be caused by a defect in the glucose transport system in the body. Thus, if a molecular mechanism controlling glucose transport system could be understood, treatment of T2DM could be possible. In the early 70s, hyperglycemia was thought to develop primarily due to a defect in the muscle and adipose tissue; thus, muscle/adipose tissue type glucose transporter (GLUT4) became a major research interest in the diabetology. However, glucose utilization occurs not only in muscle/adipose tissue but also in liver and brain. Thus, I was interested in the hepatic glucose transport system, where glucose storage and release are the most actively occurring.
Adipogenesis ; Adipose Tissue ; Animals ; Brain ; Clone Cells* ; Cloning, Organism* ; Diabetes Mellitus, Type 2 ; Glucokinase ; Gluconeogenesis ; Glucose Transport Proteins, Facilitative* ; Glucose Transporter Type 2* ; Glucose* ; Glycolysis ; Homeostasis* ; Humans ; Hyperglycemia* ; Liver ; Promoter Regions, Genetic ; Rats* ; Transcription Factors

BACKGROUND/OBJECTIVES: The anti-diabetic activity of pear through inhibition of α-glucosidase has been demonstrated. However, little has been reported about the effect of pear on insulin signaling pathway in obesity. The aims of this study are to establish pear pomace 50% ethanol extract (PPE)-induced improvement of insulin sensitivity and characterize its action mechanism in 3T3-L1 cells and high-fat diet (HFD)-fed C57BL/6 mice. MATERIALS/METHODS: Lipid accumulation, monocyte chemoattractant protein-1 (MCP-1) secretion and glucose uptake were measure in 3T3-L1 cells. Mice were fed HFD (60% kcal from fat) and orally ingested PPE once daily for 8 weeks and body weight, homeostasis model assessment of insulin resistance (HOMA-IR), and serum lipids were measured. The expression of proteins involved in insulin signaling pathway was evaluated by western blot assay in 3T3-L1 cells and adipose tissue of mice. RESULTS: In 3T3-L1 cells, without affecting cell viability and lipid accumulation, PPE inhibited MCP-1 secretion, improved glucose uptake, and increased protein expression of phosphorylated insulin receptor substrate 1 [p-IRS-1, (Tyr⁶³²)], p-Akt, and glucose transporter type 4 (GLUT4). Additionally, in HFD-fed mice, PPE reduced body weight, HOMA-IR, and serum lipids including triglyceride and LDL-cholesterol. Furthermore, in adipose tissue, PPE up-regulated GLUT4 expression and expression ratio of p-IRS-1 (Tyr⁶³²)/IRS, whereas, down-regulated p-IRS-1 (Ser³⁰⁷)/IRS. CONCLUSIONS: Our results collectively show that PPE improves glucose uptake in 3T3-L1 cells and insulin sensitivity in mice fed a HFD through stimulation of the insulin signaling pathway. Furthermore, PPE-induced improvement of insulin sensitivity was not accompanied with lipid accumulation.
3T3-L1 Cells ; Adipose Tissue ; Animals ; Blotting, Western ; Body Weight ; Cell Survival ; Chemokine CCL2 ; Diet, High-Fat ; Ethanol* ; Glucose ; Glucose Transport Proteins, Facilitative ; Glucose Transporter Type 4 ; Homeostasis ; Insulin Receptor Substrate Proteins ; Insulin Resistance* ; Insulin* ; Lipid Metabolism ; Mice ; Obesity ; Pyrus* ; Triglycerides