Anomalous transport kinetics and the glucose carrier hypothesis

Regen, David M.; Tarpley, Harold L.

doi:10.1016/0005-2736(74)90320-4

Cited by 83 publications

(48 citation statements)

References 26 publications

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“…Thus, Km for net influx is slightly underestimated and it is likely that the true K m for net influx of methylglucose (measured value 3.8 mmol/1) is not different from K m for equilibrium exchange (4.8 mmol/l). This shows that the transport system is not asymmetrical in the same way as that of human erythrocytes in which K~ for equilibrium exchange is more than 10 times higher than that for net influx [13]. "lhe measured K m for net glucose uptake (7.7 mmol/l) was twice as high as that for methylglucose, which is in agreement with the results of Ciaraldi et al [9] and Whitesell and Gliemann [2].…”

Section: Discussionsupporting

confidence: 89%

Hexose transport in human adipocytes: Factors influencing the response to insulin and kinetics of methylglucose and glucose transport

Pedersen

Gliemann

1981

Diabetologia

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Summary. Optimal experimental conditions were defined for measuring the initial uptake rate of the non-metabolizable sugar analogue 3-O-methylglucose in non-stimulated and insulin-stimulated human adipocytes. The permeability of the adipocyte plasma membrane for tracer methylglucose (100 ~tmol/l) was 2.9 • 10 -7 cm • s -1 at 37~ and slightly lower at 20~ At 37~ and pH 7.4 insulin (5nmol/l) increased the permeability about twofold (range 1.5 to fivefold) with half maximal effect at about 100 pmol/1. At pH 7.0 the dose response curve for the insulin effect on the uptake rate of methylglucose was shifted about 2.5-fold to the right. The permeability to L-glucose due to simple diffusion was estimated as 3.0 • 10-~~ cm • s-1 suggesting that uptake of methylglucose occurs almost exclusively by facilitated diffusion. The Km for methylglucose equilibrium exchange in insulin stimulated cells was about 4.8mmol/1. The initial uptake of tracer methylglucose in insulin-stimulated cells was inhibited by unlabelled methylglucose and by D-glucose with inhibition constants of about 3.8 and 7.7 mmol/ 1, respectively. Uptake of tracer 2-deoxyglucose (50 ~tmol/l) in insulin-stimulated adipocytes was linear from 10 s to 5 min whereas the rate of uptake in the presence of 3 mmol/l of D-glucose was markedly decreased suggesting that deoxyglucose uptake after a few minutes is mainly limited by hexokinase in the presence of glucose.

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Section: Discussionsupporting

confidence: 89%

Hexose transport in human adipocytes: Factors influencing the response to insulin and kinetics of methylglucose and glucose transport

Pedersen

Gliemann

1981

Diabetologia

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“…Aside from the experimental errors related to the measurement of fluxes, these deviations contribute significantly to small differences in the calculated V/Kvalues. The importance of comparing the V/K values for the different procedures while dealing with carrier systems, and especially those with asymmetric properties, has been implied in a recent review by LeFevre (2) in reference to the work of Baker and Widdas (16), Geck (17), and Wilbrandt (18), and by Regen and Tarpley (19).…”

Section: Discussionmentioning

confidence: 99%

“…We have demonstrated that unstirred layers need not be considered. In the case of the hexose transport systems of red blood cells, the asymmetric behavior of the carrier and some kinetic anomalies were attributed to something analogous to unstirred layer effects (19) although these effects were not tested directly.…”

Section: Discussionmentioning

confidence: 99%

Transport of uridine in human red blood cells. Demonstration of a simple carrier-mediated process.

Cabantchik¹,

Ginsburg²

1977

The Journal of General Physiology

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From the analysis of kinetic data we infer that the movement of the unloaded carrier is the rate-limiting step in transport of uridine. From the value of 104 uridine carrier molecules per cell we calculate the turnover rate for uridine transport to be 7,600 molecules/min for influx and 35,000 molecules/min for efflux (both at 25°C). The present work provides a unique example of an asymmetric transport mechanism which is fully consistent with the predictions of a simple carrier model. The mechanism is discussed in terms of current concepts of membrane structure. I N T R O D U C T I O NT h e h u m a n r e d b l o o d cell has for m a n y y e a r s p r o v i d e d a classical e x p e r i m e n t a l o b j e c t f o r the i n v e s t i g a t i o n o f t r a n s p o r t p h e n o m e n a in biological m e m b r a n e s . A m o n g t h e v a r i o u s t r a n s p o r t systems p r e s e n t in this cell m e m b r a n e , the system r e s p o n s i b l e f o r g l u c o s e m o v e m e n t has b e e n o n e o f the m o s t t h o r o u g h l y investig a t e d , p a r t i c u l a r l y in r e g a r d to kinetic d e s c r i p t i o n o f m o l e c u l a r e v e n t s u n d e r l y -

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“…However, due to the complexities of the erythrocyte system, differences between experimental methods and variations in kinetic data, many other models have been proposed over the same time period. 92 These models include the following: the Regen-Tarpley asymmetrical carrier model, 93 the Eilam model, 94 the lattice-pore model, 95 the tetramer model, 96 and the introversion model. 97 Despite the differences between these models, they all tried to explain two principal scenarios that occur during glucose transfer: the asymmetry of the transport affinities (K M , substrate concentration at half the maximal transport rate) of zero trans between hexose influx and efflux; and the trans-acceleration that occurs when hexose is present on the trans side.…”

Section: Long and Cheesemanmentioning

confidence: 99%

Structure of, and functional insight into the GLUT family of membrane transporters

Long¹,

Cheeseman²

2015

CHC

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This review examines the development of structure and function of the human GLUT proteins, gene family hSLC2A. These proteins are essential for moving the key metabolites, glucose, galactose, and fructose in and out of cells, as well as a number of other important substrates. Despite over five decades of research, it is still not fully understood how they work at the molecular level, although the recent publication of a crystal structure of GLUT1 sug-

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Anomalous transport kinetics and the glucose carrier hypothesis

Cited by 83 publications

References 26 publications

Hexose transport in human adipocytes: Factors influencing the response to insulin and kinetics of methylglucose and glucose transport

Hexose transport in human adipocytes: Factors influencing the response to insulin and kinetics of methylglucose and glucose transport

Transport of uridine in human red blood cells. Demonstration of a simple carrier-mediated process.

Structure of, and functional insight into the GLUT family of membrane transporters

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