Carrier-mediated fructose uptake significantly contributes to carbohydrate metabolism in human skeletal muscle

Zierath, Juleen R.; Nolte, Lorraine A.; Wahlström, Erik; Galuska, Dana; Shepherd, Peter R.; Kahn, Barbara B.; Wallberg-Henriksson, Harriet

doi:10.1042/bj3110517

Cited by 39 publications

(30 citation statements)

References 25 publications

(34 reference statements)

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“…These authors only reported data for the plasma membrane fraction but they too, did not observe any changes in GLUT5 content after treatment of human adipocytes with insulin [24]. Finally, based on biochemical and immunocytochemical evidence, the plasma membrane localisation of GLUT5 in rat adipocytes is strikingly similar to that in human skeletal muscle [32] which we, and others, have shown to take up and metabolise fructose in CB-independent manner [17,33]. All these observations strongly support our view that GLUT5 operates as a specific fructose transporter in the rat adipocyte.…”

Section: Discussionmentioning

confidence: 62%

Fructose uptake in rat adipocytes: GLUT5 expression and the effects of streptozotocin-induced diabetes

1998

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The uptake of sugars across the plasma membrane of most mammalian cells is mediated by a family of structurally related glucose transport proteins (GLUTs). To date, five major isoforms of this family have been cloned (termed GLUT1±5) [1±3] which appear to be expressed in a tissue-specific manner and which display specific modes of regulation [1]. By far the most studied is GLUT4 and much of our current understanding regarding its regulation has stemmed from studies carried out in adipocytes [4,5]. GLUT4 is the insulin-regulated glucose transporter and in the presence of low blood insulin is sequestered largely in specialised intracellular storage vesicles [6±8]. An increase in blood insulin as occurs, for example, after a meal causes a rapid translocation in GLUT4 from its intracellular storage pool to the plasma membrane. The resulting increase in cell surface GLUT4 forms the primary mechanism by which insulin induces a substantial (up to 20-fold) stimulation in cellular glucose uptake [9±11]. Diabetologia (1998) Summary Previous studies have shown that rat adipocytes possess the capacity to take up fructose by a mechanism that is distinct from that involved in the transport of glucose. In this investigation we report that rat adipocytes express the GLUT5 fructose transporter and that it is responsible for mediating a substantial component (~80 %) of the total cellular fructose uptake. This proposition is based on the finding that only 21 % of the total fructose uptake was cytochalasin B (CB) sensitive which most likely reflects transport via GLUT1 and/or GLUT4. Consistent with this suggestion we found (i) that insulin caused a small, but significant stimulation in fructose uptake (~35 %) which was abolished in the presence of CB and (ii) that 3-O-methyl glucose inhibited fructose uptake to a level comparable with that observed in the presence of CB. GLUT5 was found to be localised only in the adipocyte plasma membrane and, unlike GLUT4 or GLUT1, its cell surface abundance was not modulated by insulin. GLUT5 expression fell substantially (by~75 %) in adipocytes of streptozotocin-diabetic rats and was accompanied by a reduction in fructose uptake by approximately 50 %. Treatment of streptozotocin-diabetic rats with sodium orthovanadate for a period of 3 days led to a significant reduction in blood glycaemia by approximately 40 % and a partial restoration in both GLUT5 expression and adipocyte fructose uptake. We suggest that fructose uptake in rat adipocytes is principally mediated by GLUT5 in an insulin-and CB-insensitive manner and that expression of GLUT5 in rat adipocytes may be regulated by changes in blood glycaemia. [Diabetologia (1998) 41: 821±828]

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Section: Discussionmentioning

confidence: 62%

Fructose uptake in rat adipocytes: GLUT5 expression and the effects of streptozotocin-induced diabetes

1998

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“…FBPase activity is indirectly regulated by cAMP, which increases in vivo in the kidney epithelia exposed to fructose compared with those exposed to glucose. It has been demonstrated in vivo that cAMP modulates fructose transport induced by fructose without affecting GLUT5 mRNA abundance (65), whereas in vitro, cAMP affects GLUT5 mRNA expression levels and is involved in GLUT5 regulation in kidney epithelia (67)(68)(69)(70).…”

Section: Discussionmentioning

confidence: 99%

Fructose transporter Glut5 expression in clear renal cell carcinoma

Villaamil

Gallego²,

Rubira³

et al. 2011

Oncol Rep

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Abstract. Renal cell carcinomas (RCC) can be subclassified for general purposes into clear cell, papillary cell, chromophobe cell carcinomas and oncocytomas. Other tumours such as collecting duct, medullary, mucinous tubular and spindle cell and associated with Xp 11.2 translocations/TFE 3 gene fusion, are much less common. There is also a residual group of unclassified cases. Previous studies have shown that RCC has high glycolytic rates, and expresses GLUT transporters, but no distinction has been made among the different subtypes of renal cell tumours and their grades of malignancy. In clear renal cell carcinoma (cRCC) glycogen levels increase, glycolysis is activated and gluconeogenesis is reduced. The clear cell subtype of RCC is characterized histologically by a distinctive pale, glassy cytoplasm and this appearance of cRCC is due to abnormalities in carbohydrate and lipid metabolism, and this abnormality results in glycogen and sterol storage. Several isoforms of glucose carriers (GLUTs) have been identified. We show here in a panel of 80 cRCC samples a significant correlation between isoform 5 (GLUT5) and many pathological parameters such as grade of differentiation, pelvis invasion and breaking capsule. GLUT5 expression also appears to associate more strongly with the clear cell RCC subtype. These data suggest a role for the GLUT5 isoform in fructose uptake that takes place in cRCC cells and which subsequently leads to the malignant RCC progression.

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“…The expression of GLUT5 in human muscle has been linked to the ability of muscle to utilize fructose for glycolysis and glycogenesis independent of GLUT4 and GLUT1 (Ref. 124 and for a review, see Ref. 125).…”

Section: Glut5mentioning

confidence: 99%

What we know about facilitative glucose transporters: Lessons from cultured cells, animal models, and human studies

Gorovits

Charron

2003

Biochem Molecular Bio Educ

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Glucose uptake by all cells in the organism by glucose transport proteins is among the most essential processes in life. The process of glucose uptake into tissues is performed by glucose transporters. This review focuses on the biology of facilitative glucose transporters (GLUTs). The knowledge that has accumulated for more than a decade with respect to the regulation of GLUT expression and function in various experimental conditions points to the great potential for GLUTs to be utilized as targets for designing therapies for treatment of diseases related to impaired regulation of glucose homeostasis including type 2 diabetes.Keywords: Glucose uptake, GLUT, insulin action, diabetes.The entry of glucose into cells is a crucial step in lifesupporting processes since glucose is the main monosaccharide in nature that provides carbon and energy for almost all cells. The passage of glucose into cells depends on different parameters, including expression of the appropriate glucose transporters in the target tissues and hormonal regulation of their function. Single cell eucaryotes such as Saccharomyces cerevisiae possess 20 genes encoding glucose or glucose-like transporters and express the glucose transporters most appropriate for the amount of glucose available [1]. In mammalian cells a tight regulation of blood glucose levels is needed to meet the energetic demands of the brain, a tissue that uses glucose as its primary energy source [2,3]. Adequate glucose flux into tissues provides maintenance of glucose homeostasis that is critical in well being. Transport of glucose across the plasma membrane is accomplished by two families of glucose transporters: sodium-glucose co-transporters (SGLT 1 1-3), mainly expressed in the apical membrane of renal and intestinal absorptive epithelial cells that transport glucose against its concentration gradient and utilize ATP (for a review, see Ref. 4), and facilitative glucose transporters (GLUTs) that are expressed in all cells that transport glucose down a concentration gradient [5][6][7]. Until now the search for the mammalian facilitative glucose transporters has yielded 12 carriers including GLUT1-5 and the recently discovered GLUT6 -12. GLUT1-4 share greater than 40% homology [8], and GLUT5, which is a fructose transporter, exhibits 42, 40, 38, and 41.6% identity with GLUT1, GLUT2, GLUT3, and GLUT4, respectively [9]. All GLUTs have been predicted to have 12 membrane-spanning domains (helices) connected by hydrophilic loops, the first of which is exofacial and contains an N-glycosylation site in GLUT1-5 (Fig. 1) [8,10]. Both the amino and carboxyl termini of GLUTs reside on the cytoplasmic side of the cell membrane [11]. The carboxyl termini of all GLUTs have unique amino acid sequences that have been utilized for development of reagents. The common sensitivity of the GLUT family to the inhibitory action of the fungal metabolite cytochalasin B has been reported widely and is utilized in studies of hexose transporters [12]. Substrate selectivity of GLUTs is dictated by conserve...

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Carrier-mediated fructose uptake significantly contributes to carbohydrate metabolism in human skeletal muscle

Cited by 39 publications

References 25 publications

Fructose uptake in rat adipocytes: GLUT5 expression and the effects of streptozotocin-induced diabetes

Fructose uptake in rat adipocytes: GLUT5 expression and the effects of streptozotocin-induced diabetes

Fructose transporter Glut5 expression in clear renal cell carcinoma

What we know about facilitative glucose transporters: Lessons from cultured cells, animal models, and human studies

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