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

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

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

BACKGROUND/OBJECTIVES: Recent living condition improvements, changes in dietary habits, and reductions in physical activity are contributing to an increase in metabolic syndrome symptoms including diabetes and obesity. Through such societal developments, humankind is continuously exposed to metabolic diseases such as diabetes, and the number of the victims is increasing. This study investigated Cordyceps militaris water extract (CMW)-induced glucose uptake in HepG2 cells and the effect of CMW treatment on glucose metabolism. MATERIALS/METHODS: Colorimetric assay kits were used to determine the glucokinase (GK) and pyruvate dehydrogenase (PDH) activities, glucose uptake, and glycogen content. Either RT-PCR or western blot analysis was performed for quantitation of glucose transporter 2 (GLUT2), hepatocyte nuclear factor 1 alpha (HNF-1α), phosphatidylinositol 3-kinase (PI3k), protein kinase B (Akt), phosphorylated AMP-activated protein kinase (pAMPK), phosphoenolpyruvate carboxykinase, GK, PDH, and glycogen synthase kinase 3 beta (GSK-3β) expression levels. The α-glucosidase inhibitory activities of acarbose and CMW were evaluated by absorbance measurement. RESULTS: CMW induced glucose uptake in HepG2 cells by increasing GLUT2 through HNF-1α expression stimulation. Glucose in the cells increased the CMW-induced phosphorylation of AMPK. In turn, glycolysis was stimulated, and glyconeogenesis was inhibited. Furthermore, by studying the mechanism of action of PI3k, Akt, and GSK-3β, and measuring glycogen content, the study confirmed that the glucose was stored in the liver as glycogen. Finally, CMW resulted in a higher level of α-glucosidase inhibitory activity than that from acarbose. CONCLUSION: CMW induced the uptake of glucose into HepG2 cells, as well, it induced metabolism of the absorbed glucose. It is concluded that CMW is a candidate or potential use in diabetes prevention and treatment.
Acarbose ; alpha-Glucosidases* ; AMP-Activated Protein Kinases ; Blotting, Western ; Cordyceps* ; Food Habits ; Glucokinase ; Glucose Transport Proteins, Facilitative ; Glucose* ; Glycogen ; Glycogen Synthase Kinase 3 ; Glycolysis ; Hep G2 Cells* ; Hepatocyte Nuclear Factor 1-alpha ; Hypoglycemic Agents ; Liver ; Metabolic Diseases ; Metabolism* ; Motor Activity ; Obesity ; Oxidoreductases ; Phosphatidylinositol 3-Kinase ; Phosphoenolpyruvate ; Phosphorylation ; Proto-Oncogene Proteins c-akt ; Pyruvic Acid ; Social Conditions ; Water*

Objective To establish a Daphnia model of alloxan-induced diabetes. Methods Daphnia were exposed to three different concentrations of alloxan (3, 5, and 10 mmol/L) for 30 minutes. Blood glucose and survival rate were recorded for 72 hours after alloxan insult. Sequence analysis and phylogenetic inference for glucose transporters (GLUT) were clustered with the maximum-likelihood method. Using reverse transcription and quantitative polymerase chain reaction techniques, we investigated the transcriptional changes of GLUT at 12 hours after alloxan (5 mmol/L) exposure. Results Compared with control, 3 mmol/L, and 5 mmol/L as well as 10 mmol/L alloxan initially induced transient blood glucose decline by 15% for 2 hours and 12 hours respectively. In Daphnia with 5 and 10 mmol/L alloxan, their blood glucose was persistently raised by about 150% since after 24-hour insult. Survival rate of Daphnia exposure to alloxan with concentrations of 3, 5, and 10 mmol/L were 90%, 75%, and 25% respectively. We predicted seven GLUT genes in the Daphnia genome and successfully amplified them using real-time polymerase chain reaction. Two of seven GLUT transcripts were down-regulated in Daphnia with 5 mmol/L alloxan-induced diabetes. Conclusion Alloxan-induced diabetes model was successfully established in the Daphnia pulex, suggesting diabetes-relevant experiments can be conducted using Daphnia.
Alloxan ; Animals ; Blood Glucose ; analysis ; Daphnia ; Diabetes Mellitus, Experimental ; chemically induced ; physiopathology ; Disease Models, Animal ; Gene Expression Regulation ; Glucose Transport Proteins, Facilitative ; genetics ; metabolism ; Likelihood Functions ; Phylogeny ; Real-Time Polymerase Chain Reaction

BACKGROUND: Previous studies have shown that 17beta-estradiol activates AMP-activated protein kinase (AMPK) in rodent muscle and C2C12 myotubes and that acute 17beta-estradiol treatment rapidly increases AMPK phosphorylation possibly through non-genomic effects but does not stimulate glucose uptake. Here, we investigated whether 24-hour 17beta-estradiol treatment stimulated glucose uptake and regulated the expression of genes associated with glucose and energy metabolism through the genomic effects of estrogen receptor (ER) in C2C12 myotubes. METHODS: C2C12 myotubes were treated with 17beta-estradiol for 24 hours, and activation of AMPK, uptake of glucose, and expression of genes encoding peroxisome proliferator-activated receptor γ coactivator 1α, carnitine palmitoyltransferase 1β, uncoupling protein 2, and glucose transporter 4 were examined. Furthermore, we investigated whether AMPK inhibitor (compound C) or estrogen receptor antagonist (ICI182.780) treatment reversed 17beta-estradiol-induced changes. RESULTS: We found that 24-hour treatment of C2C12 myotubes with 17beta-estradiol stimulated AMPK activation and glucose uptake and regulated the expression of genes associated with glucose and energy metabolism. Treatment of C2C12 myotubes with the estrogen receptor antagonist (ICI182.780) reversed 17beta-estradiol-induced AMPK activation, glucose uptake, and changes in the expression of target genes. Furthermore, treatment with the AMPK inhibitor (compound C) reversed 17beta-estradiol-induced glucose uptake and changes in the expression of target genes. CONCLUSION: Our results suggest that 17beta-estradiol stimulates AMPK activation and glucose uptake and regulates the expression of genes associated with glucose and energy metabolism in C2C12 myotubes through the genomic effects of ER.
AMP-Activated Protein Kinases ; Carnitine O-Palmitoyltransferase ; Energy Metabolism ; Estrogens ; Glucose Transport Proteins, Facilitative ; Glucose ; Muscle Fibers, Skeletal ; Peroxisomes ; Phosphorylation ; Rodentia

BACKGROUND/OBJECTIVES: Recently, anthocyanins have been reported to have various biological activities. Furthermore, anthocyanin-rich purple corn extract (PCE) ameliorated insulin resistance and reduced diabetes-associated mesanginal fibrosis and inflammation, suggesting that it may have benefits for the prevention of diabetes and diabetes complications. In this study, we determined the anthocyanins and non-anthocyanin component of PCE by HPLC-ESI-MS and investigated its anti-diabetic activity and mechanisms using C57BL/KsJ db/db mice. MATERIALS/METHODS: The db/db mice were divided into four groups: diabetic control group (DC), 10 or 50 mg/kg PCE (PCE 10 or PCE 50), or 10 mg/kg pinitol (pinitol 10) and treated with drugs once per day for 8 weeks. During the experiment, body weight and blood glucose levels were measured every week. At the end of treatment, we measured several diabetic parameters. RESULTS: Compared to the DC group, Fasting blood glucose levels were 68% lower in PCE 50 group and 51% lower in the pinitol 10 group. Furthermore, the PCE 50 group showed 2- fold increased C-peptide and adiponectin levels and 20% decreased HbA1c levels, than in the DC group. In pancreatic islets morphology, the PCE- or pinitol-treated mice showed significant prevention of pancreatic beta-cell damage and higher insulin content. Microarray analyses results indicating that gene and protein expressions associated with glycolysis and fatty acid metabolism in liver and fat tissues. In addition, purple corn extract increased the phosphorylation of AMP-activated protein kinase (AMPK) and decreased phosphoenolpyruvate carboxykinase (PEPCK), glucose 6-phosphatase (G6pase) genes in liver, and also increased glucose transporter 4 (GLUT4) expressions in skeletal muscle. CONCLUSIONS: Our results suggested that PCE exerted anti-diabetic effects through protection of pancreatic beta-cells, increase of insulin secretion and AMPK activation in the liver of C57BL/KsJ db/db mice.
Adiponectin ; AMP-Activated Protein Kinases ; Animals ; Anthocyanins ; Blood Glucose ; Body Weight ; C-Peptide ; Diabetes Complications ; Fasting ; Fibrosis ; Glucose Transport Proteins, Facilitative ; Glucose-6-Phosphatase ; Glycolysis ; Inflammation ; Insulin ; Insulin Resistance ; Islets of Langerhans ; Liver ; Metabolism ; Mice* ; Muscle, Skeletal ; Phosphoenolpyruvate ; Phosphorylation ; Zea mays*

Previous studies have shown that ginsenoside Rb1 (Rb1), one of active components in ginseng, can activate insulin signaling pathway and promote translocation of glucose transporters (GLUTs) to increase glucose uptake in adipocytes. However, the effect of Rb1 on the expressions of GLUTs remains unknown. In this study, the effects of Rb1 on GLUT1 and GLUT4 were observed in 3T3-L1 adipocytes and epididymal adipose tissue of db/db obese diabetic mice. Male db/db mice were treated with Rb1 by intraperitoneal injection at the dosage of 20 mg x kg(-1) for 14 d. Rb1 reduced HOMA-IR significantly (P < 0.05, n = 5), and FBG and FINS sowed declining trend after treatment with Rb1. Rb1 recovered the expressions of GLUT1 and GLUT4 and phosphorylation of AKT in adipose tissue of db/db mice. In vitro, glucose consumption in 3T3-L1 adipocytes treated with 10 micromol x L(-1) Rb1 for 24 h was elevated (P < 0.05, n=3), and mRNA of GLUT1 and GLUT4 were up-regulated (P < 0.05, n=3) and proteins of GLUT1 and GLUT4 were also increased. AKT was activated in adipocytes treated with Rb1 for 3 h. It can be concluded that ginsenoside Rb1 can up-regulate the expression of GLUTs in adipose tissue, in addition to activate insulin signalling pathway, which may partially account for its insulin sensitizing activity and regulating effect of glucose metabolism.
3T3 Cells ; Adipocytes ; drug effects ; Animals ; Cell Line ; Diabetes Mellitus, Experimental ; metabolism ; Ginsenosides ; pharmacology ; Glucose ; metabolism ; Glucose Transport Proteins, Facilitative ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Up-Regulation ; drug effects

Fanconi-Bickel syndrome is a rare autosomal recessive disorder caused by a mutation in the facilitative glucose transporter 2 gene (GLUT2 or SLC2A2 gene) that codes for the glucose transporter protein 2 expressed in hepatocytes, pancreatic beta-cells, enterocytes, and renal tubular cells. Mutation of this gene leads to defective carbohydrate metabolism, hepatomegaly, glucose intolerance, proximal renal tubular dysfunction, and hypophosphatemic rickets. We report a case of Fanconi-Bickel syndrome in an 18-year-old man who presented due to renal glycosuria; a mutation was identified in the GLUT2 gene (c.482C > A + c.1556G > A). To the best of our knowledge, unlike previous reports of Fanconi-Bickel syndrome, this case was relatively unusual in that it caused only mild clinical signs.
Carbohydrate Metabolism ; Enterocytes ; Fanconi Syndrome ; Glucose Intolerance ; Glucose Transport Proteins, Facilitative ; Glucose Transporter Type 2 ; Hepatocytes ; Hepatomegaly ; Hypophosphatemic Rickets, X-Linked Dominant

AIM: The present study was undertaken to characterize the effects of Wuling San on urate excretion and renal function, and explore its possible mechanisms of action in hyperuricemic mice. METHODS: Mice were administered with 250 mg·kg(-1) potassium oxonate by gavage once daily (10 animals/group) for seven consecutive days to develop a hyperuricemia model. Different doses of Wuling powder were orally initiated on the day 1 h after oxonate was given, separately. Allopurinol was used as a positive control. Serum and urine levels of uric acid and creatinine, and fractional excretion of uric acid (FEUA) were measured in hyperuricemic mice treated with Wuling San and allopurinol. Simultaneously, renal mRNA and protein levels of urate transporter 1 (mURAT1), glucose transporter 9 (mGLUT9), organic anion transporter 1 (mOAT1), as well as organic cation/carnitine transporters mOCT1, mOCT2 and mOCTN2, were assayed by semi-quantitative RT-PCR and Western blot methods, respectively. RESULTS AND CONCLUSION Compared to the hyperuricemia control group, Wuling San significantly reduced serum uric acid and creatinine levels, increased 24 h urate and creatinine excretion, and FEUA in hyperuricemic mice, exhibiting its ability to enhance urate excretion and improve kidney function. Wuling San was found to down-regulate mRNA and protein levels of mURAT1 and mGLUT9, as well as up-regulate mOAT1 in the kidney of hyperuricemic mice. Moreover, Wuling San up-regulated renal mRNA and protein levels of mOCT1, mOCT2 and mOCTN2, leading to kidney protection in this model.
Animals ; Drugs, Chinese Herbal ; administration & dosage ; Glucose Transport Proteins, Facilitative ; genetics ; metabolism ; Humans ; Hyperuricemia ; drug therapy ; genetics ; metabolism ; Kidney ; drug effects ; metabolism ; Male ; Mice ; Organic Anion Transport Protein 1 ; genetics ; metabolism ; Organic Anion Transporters ; genetics ; metabolism ; Up-Regulation ; drug effects ; Uric Acid ; metabolism