Glucose transporter 5 is undetectable in outer hair cells and does not contribute to cochlear amplification

Wu, Xudong; Wei, Xiang; Gao, Jiangang; Yu, Yiling; Song, Jia; Zheng, Jing; Dallos, Peter; He, David Z.Z.; Cheatham, Mary Ann; Zuo, Jian

doi:10.1016/j.brainres.2008.02.094

Cited by 13 publications

(12 citation statements)

References 40 publications

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“…Generation of GLUT5‐KO (19), KHK‐KO (20), and Rab11a ΔIEC (12) mice was described in detail previously. Genetic modifications in these mice have been validated using primer sequences in (12, 19, 20). Although GLUT5‐KO and KHK‐KO mice showed normal phenotypes if fed fructose‐free diets, Rab11a ΔIEC mice exhibited ranting and growth retardation.…”

Section: Methodsmentioning

confidence: 99%

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Transport, metabolism, and endosomal trafficking‐dependent regulation of intestinal fructose absorption

Patel

Douard

et al. 2015

FASEB j.

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Dietary fructose that is linked to metabolic abnormalities can up-regulate its own absorption, but the underlying regulatory mechanisms are not known. We hypothesized that glucose transporter (GLUT) protein, member 5 (GLUT5) is the primary fructose transporter and that fructose absorption via GLUT5, metabolism via ketohexokinase (KHK), as well as GLUT5 trafficking to the apical membrane via the Ras-related protein-in-brain 11 (Rab11)a-dependent endosomes are each required for regulation. Introducing fructose but not lysine and glucose solutions into the lumen increased by 2- to 10-fold the heterogeneous nuclear RNA, mRNA, protein, and activity levels of GLUT5 in adult wild-type mice consuming chow. Levels of GLUT5 were >100-fold that of candidate apical fructose transporters GLUTs 7, 8, and 12 whose expression, and that of GLUT 2 and the sodium-dependent glucose transporter protein 1 (SGLT1), was not regulated by luminal fructose. GLUT5-knockout (KO) mice exhibited no facilitative fructose transport and no compensatory increases in activity and expression of SGLT1 and other GLUTs. Fructose could not up-regulate GLUT5 in GLUT5-KO, KHK-KO, and intestinal epithelial cell-specific Rab11a-KO mice. The fructose-specific metabolite glyceraldehyde did not increase GLUT5 expression. GLUT5 is the primary transporter responsible for facilitative absorption of fructose, and its regulation specifically requires fructose uptake and metabolism and normal GLUT5 trafficking to the apical membrane.

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Section: Methodsmentioning

confidence: 99%

“…WT (129/B6) mice used for the Rab11a DIEC experiment were same-age littermates. Generation of GLUT5-KO (19), KHK-KO (20), and Rab11a DIEC (12) mice was described in detail previously. Genetic modifications in these mice have been validated using primer sequences in (12,19,20).…”

Section: Animalsmentioning

confidence: 99%

Transport, metabolism, and endosomal trafficking‐dependent regulation of intestinal fructose absorption

Patel

Douard

et al. 2015

FASEB j.

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“…Study IC was conducted using GLUT5 Ϫ/Ϫ mice (background: C57BL6) donated by J. Zuo, St. Jude's Children's Research Hospital (47). Because the breeding of GLUT5 Ϫ/Ϫ produced small litters (2-4 pups) that were disproportionately female, only 10 male mice of similar age were produced from a large number of breeders.…”

Section: Animals and Experimental Designsmentioning

confidence: 99%

Effect of dietary fructose on portal and systemic serum fructose levels in rats and in KHK^−/−and GLUT5^−/−mice

Patel

Sugimoto

Douard

et al. 2015

American Journal of Physiology-Gastrointestinal and Liver Physi

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Elevated blood fructose concentrations constitute the basis for organ dysfunction in fructose-induced metabolic syndrome. We hypothesized that diet-induced changes in blood fructose concentrations are regulated by ketohexokinase (KHK) and the fructose transporter GLUT5. Portal and systemic fructose concentrations determined by HPLC in wild-type mice fed for 7 days 0% free fructose were <0.07 mM, were independent of time after feeding, were similar to those of GLUT5(-/-), and did not lead to hyperglycemia. Postprandial fructose levels, however, increased markedly in those fed isocaloric 20% fructose, causing significant hyperglycemia. Deletion of KHK prevented fructose-induced hyperglycemia, but caused dramatic hyperfructosemia (>1 mM) with reversed portal to systemic gradients. Systemic fructose in wild-type and KHK(-/-) mice changed by 0.34 and 1.8 mM, respectively, for every millimolar increase in portal fructose concentration. Systemic glucose varied strongly with systemic, but not portal, fructose levels in wild-type, and was independent of systemic and portal fructose in KHK(-/-), mice. With ad libitum feeding for 12 wk, fructose-induced hyperglycemia in wild-type, but not hyperfructosemia in KHK(-/-) mice, increased HbA1c concentrations. Increasing dietary fructose to 40% intensified the hyperfructosemia of KHK(-/-) and the fructose-induced hyperglycemia of wild-type mice. Fructose perfusion or feeding in rats also caused duration- and dose-dependent hyperfructosemia and hyperglycemia. Significant levels of blood fructose are maintained independent of dietary fructose, KHK, and GLUT5, probably by endogenous synthesis of fructose. KHK prevents hyperfructosemia and fructose-induced hyperglycemia that would markedly increase HbA1c levels. These findings explain the hyperfructosemia of human hereditary fructosuria as well as the hyperglycemia of fructose-induced metabolic syndrome.

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“…Ϫ/Ϫ mice were generated as described (34). Briefly, a Glut5-floxed construct was generated by inserting one loxP site upstream of the predicted promoter and exon 1 and another loxP site downstream of exon 4 of the Glut5 gene, which has 14 exons.…”

Section: Animal Models and Experimental Diets-glut5mentioning

confidence: 99%

“…Briefly, a Glut5-floxed construct was generated by inserting one loxP site upstream of the predicted promoter and exon 1 and another loxP site downstream of exon 4 of the Glut5 gene, which has 14 exons. After establishing germ line transmission, intercrosses between Glut5 floxed/ϩ and a ubiquitous Cre-expressing line EIIA-Cre (35) resulted in offspring with the expected global deletion of the floxed exons 1-4 of Glut5 (34). Glut5…”

Section: Animal Models and Experimental Diets-glut5mentioning

confidence: 99%

Slc2a5 (Glut5) Is Essential for the Absorption of Fructose in the Intestine and Generation of Fructose-induced Hypertension

Barone

Fussell

Singh

et al. 2009

Journal of Biological Chemistry

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209

193

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The identity of the transporter responsible for fructose absorption in the intestine in vivo and its potential role in fructose-induced hypertension remain speculative. Here we demonstrate that Glut5 (Slc2a5) deletion reduced fructose absorption by ϳ75% in the jejunum and decreased the concentration of serum fructose by ϳ90% relative to wild-type mice on increased dietary fructose. When fed a control (60% starch) diet, Glut5 ؊/؊ mice had normal blood pressure and displayed normal weight gain. However, whereas Glut5 ؉/؉ mice showed enhanced salt absorption in their jejuna in response to luminal fructose and developed systemic hypertension when fed a high fructose (60% fructose) diet for 14 weeks, Glut5 ؊/؊ mice did not display fructose-stimulated salt absorption in their jejuna, and they experienced a significant impairment of nutrient absorption in their intestine with accompanying hypotension as early as 3-5 days after the start of a high fructose diet. Examination of the intestinal tract of Glut5 ؊/؊ mice fed a high fructose diet revealed massive dilatation of the caecum and colon, consistent with severe malabsorption, along with a unique adaptive up-regulation of ion transporters. In contrast to the malabsorption of fructose, Glut5 ؊/؊ mice did not exhibit an absorption defect when fed a high glucose (60% glucose) diet. We conclude that Glut5 is essential for the absorption of fructose in the intestine and plays a fundamental role in the generation of fructose-induced hypertension. Deletion of Glut5 results in a serious nutrient-absorptive defect and volume depletion only when the animals are fed a high fructose diet and is associated with compensatory adaptive up-regulation of ion-absorbing transporters in the colon.

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Glucose transporter 5 is undetectable in outer hair cells and does not contribute to cochlear amplification

Cited by 13 publications

References 40 publications

Transport, metabolism, and endosomal trafficking‐dependent regulation of intestinal fructose absorption

Transport, metabolism, and endosomal trafficking‐dependent regulation of intestinal fructose absorption

Effect of dietary fructose on portal and systemic serum fructose levels in rats and in KHK^−/−and GLUT5^−/−mice

Slc2a5 (Glut5) Is Essential for the Absorption of Fructose in the Intestine and Generation of Fructose-induced Hypertension

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Glucose transporter 5 is undetectable in outer hair cells and does not contribute to cochlear amplification

Cited by 13 publications

References 40 publications

Transport, metabolism, and endosomal trafficking‐dependent regulation of intestinal fructose absorption

Transport, metabolism, and endosomal trafficking‐dependent regulation of intestinal fructose absorption

Effect of dietary fructose on portal and systemic serum fructose levels in rats and in KHK−/−and GLUT5−/−mice

Slc2a5 (Glut5) Is Essential for the Absorption of Fructose in the Intestine and Generation of Fructose-induced Hypertension

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Effect of dietary fructose on portal and systemic serum fructose levels in rats and in KHK^−/−and GLUT5^−/−mice