Is phloretin the sugar transport inhibitor in intestine?

Diedrich, Donald F.

doi:10.1016/0003-9861(68)90292-0

Cited by 50 publications

(11 citation statements)

References 28 publications

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“…Phloretin was subsequently found to block sugar uptake in intestinal tissue [51], drawing significant interest to its application in the treatment of diabetes. Phloretin was shown to specifically inhibit GLUT2 and to a lesser extent SGLT1 [22,52].…”

Section: Discussionmentioning

confidence: 99%

Live imaging of GLUT2 glucose-dependent trafficking and its inhibition in polarized epithelial cysts

et al. 2014

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GLUT2 is a facilitative glucose transporter, expressed in polarized epithelial cells of the liver, intestine, kidney and pancreas, where it plays a critical role in glucose homeostasis. Together with SGLT1/2, it mediates glucose absorption in metabolic epithelial tissues, where it can be translocated apically upon high glucose exposure. To track the subcellular localization and dynamics of GLUT2, we created an mCherry–hGLUT2 fusion protein and expressed it in multicellular kidney cysts, a major site of glucose reabsorption. Live imaging of GLUT2 enabled us to avoid the artefactual localization of GLUT2 in fixed cells and to confirm the apical GLUT2 model. Live cell imaging showed a rapid 15 ± 3 min PKC-dependent basal-to-apical translocation of GLUT2 in response to glucose stimulation and a fourfold slower basolateral translocation under starvation. These results mark the physiological importance of responding quickly to rising glucose levels. Importantly, we show that phloretin, an apple polyphenol, inhibits GLUT2 translocation in both directions, suggesting that it exerts its effect by PKC inhibition. Subcellular localization studies demonstrated that GLUT2 is endocytosed through a caveolae-dependent mechanism, and that it is at least partly recovered in Rab11A-positive recycling endosome. Our work illuminates GLUT2 dynamics, providing a platform for drug development for diabetes and hyperglycaemia.

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Section: Discussionmentioning

confidence: 99%

Live imaging of GLUT2 glucose-dependent trafficking and its inhibition in polarized epithelial cysts

et al. 2014

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“…Stifling (1967) and Diedrich (1968) also estimated, again without correction for nonspecific binding, the number of transporters per cell of hamster intestine as 2.6 • 106 -4 x 108, while Wright and Peerce (1985) gave an estimate of 105-106 transporters per cell of rabbit intestine. From our data we estimate about 106-107 transporters per cell in mice on a high-carbohydrate diet, and about 1014-1015 transporters for the whole length of the mouse small intestine.…”

Section: The Positional Gradient Of Glucose Transportmentioning

confidence: 99%

Use of phlorizin binding to demonstrate induction of intestinal glucose transporters

Ferraris¹,

Diamond²

1986

J. Membrain Biol.

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We used specific binding of phlorizin to the intact intestinal mucosa in order to measure glucose transport site density in intestines of mice fed a high-carbohydrate or no-carbohydrate diet. Nonspecific binding varied with intestinal position but showed only modest dependence on diet. Specific binding to glucose transporters was 1.9 times greater in jejunum of high-carbohydrate mice than of no-carbohydrate mice; this ratio was the same as the ratio for Vmax values of active D-glucose uptake between the two diet groups. The gradient in specific binding of phlorizin along the intestine paralleled the gradient in Vmax of glucose transport. These results directly demonstrate that the increase in intestinal glucose transport caused by a high-carbohydrate diet is due to induction of glucose transporters. They also indicate that the normal positional gradient in glucose transport along the intestine arises from a gradient in transporters, induced by the normal gradient in luminal glucose concentration.

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“…Ethanol extracts of the tissue and also of the incubating solution were then analyzed by thin-layer chromatography with two systems: a nonpolar silica gel system whose solvent consisted of ethanol/chloroform/butanol (26 : 60 : 4 vol/ vol), and a polar cellulose system whose solvent consisted of ethanol/acetic acid/water (20 : 1 : 80 vol/vol; Diedrich, 1968). In the former, phloretin travelled close to the solvent front (Rf = 0.9) while phlorizin stayed close to the origin (Rf = 0.1); the second system effected the opposite migration pattern (Rf for phloretin -0.1, phlorizin -0.6).…”

Section: Thin-layer Chromatographymentioning

confidence: 99%

“…First, although equilibrium binding of phlorizin is rapid in whole tissue (Diedrich, 1968), the incubation should still be long enough to Fig. 1.…”

Section: Choice Of Incubation Timementioning

confidence: 99%

A method for measuring apical glucose transporter site density in intact intestinal mucosa by means of phlorizin binding

Ferraris¹,

Diamond²

1986

J. Membrain Biol.

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Phlorizin binding has been widely used to estimate the site density of glucose transporters on intestinal and renal brush-border vesicles. Glucose transport measurements in the intact intestinal mucosa show that changes in transport rate postulated to arise from changes in site density occur under many physiological and pathological conditions. Exploring the basis of these regulatory phenomena would be facilitated by comparing changes in transport rate and site density measured in the same preparation. Hence we developed methods for measuring phlorizin binding in everted sleeves of intact mouse intestine. Specific binding of phlorizin to glucose carriers reached an asymptotic value within 120 sec, while nonspecific binding continued to rise thereafter. Hence we used 120-sec incubations. The rate of dissociation of specifically bound phlorizin was accelerated by Na+-free solutions and even more by 50 mM glucose, while the rate of dissociation of nonspecifically bound phlorizin was independent of these solution changes. Hence we chose a 20-sec rinse in Ringer + 50 mM mannitol, because it washes out 30-40% of the nonspecifically bound phlorizin but virtually none of the specifically bound phlorizin. Ligand-binding analysis of specific binding against phlorizin concentration suggested two classes of binding sites, of which the one with stronger affinity for phlorizin probably has the higher capacity for glucose transport in mouse jejunum. The calculated affinity and capacity of this component are independent of whether one estimates the specific component of total binding by adding glucose or by removing Na+.

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Is phloretin the sugar transport inhibitor in intestine?

Cited by 50 publications

References 28 publications

Live imaging of GLUT2 glucose-dependent trafficking and its inhibition in polarized epithelial cysts

Live imaging of GLUT2 glucose-dependent trafficking and its inhibition in polarized epithelial cysts

Use of phlorizin binding to demonstrate induction of intestinal glucose transporters

A method for measuring apical glucose transporter site density in intact intestinal mucosa by means of phlorizin binding

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