The effects of cadmium on facilitative glucose transporter function In rat adipocytes were studied. A short (30 min) incubation with cadmium resulted in stimulation of 3-O-methyl-D-glucose (3OMG ) equilibrium exchange in rat adipocytes as much as four-fold. The stimulation was a saturable function of cadmium concentation with the half-maximal effect at approximately 0.5 mM CdS04. The stimulation was due to an increase in Vmax with no significant changes in KM. No further stimulation of 30MG flux was observed once adipocytes were maximally stimulated by insulin. Semiquantitative immunoblot analysis of subcellular fractions revealed that the stimulation was accompanied by an insignificant and only a modest (less than 50%) increase in plasma membrane GLUT4 and GLUT1 levels, respectively, suggesting that the stimulation involves largely an increased catalytic activity of either or both of GLUTI and GLUT4. We next studied effect of cadmium on GLUT1 selectively using human erythrocytes and purified GLUT1 reconstituted in liposomes. With purified GLUTI, cadmium inhibited cytochalasin B binding and stimulated 30MG flux, indicating that cadmium directly interacts with GLUTI. Cadmium, however, did not affect the 30MG flux in intact human erythrocytes or their resealed ghosts. These findings strongly suggest that cadmium stimulates the catalytic activity of GLUT1 and GLUT4 in adipocytes, and this effect is suppressed by a cell-specific factor or factors in human erythrocytes.
On the basis of details of the three-dimensional structures of beta-D-glucose and of cytochalasins, either previously published or reported here (cytochalasin A), we propose a model to explain the observed difference in activity of cytochalasins in the inhibition of glucose transport. In our model cytochalasin B binds to the glucose carrier through hydrogen bonds at N2 (donates), O7 (accepts), and O23 (accepts) analogous to O6, O3, and O1, respectively, on beta-D-glucose. The hydrophobic region from C13 to C19 is also essential in binding and appears to act as an anchor in a hydrophobic domain of the glucose carrier. The presence of hydrophilic groups in this essential hydrophobic region accounts, at least in part, for the inactivity of the other cytochalasins in the series.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStructural basis of human erythrocyte glucose transporter function: pH effects on intrinsic fluorescenceJames J. Chin, Byung H. Jhun, and Chan Y. JungCite this: Biochemistry 1992, 31, 7, 1945–1951Publication Date (Print):February 1, 1992Publication History Published online1 May 2002Published inissue 1 February 1992https://pubs.acs.org/doi/10.1021/bi00122a007https://doi.org/10.1021/bi00122a007research-articleACS PublicationsRequest reuse permissionsArticle Views86Altmetric-Citations21LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
INTRODUCTION: People suffering Down syndrome have many problems that are associated with atrophy of their muscles. Because of this atrophy they tend to walk flat footed and over abduct during the initial part of the swing phase, also they tend to over-flex both at the hip and knee joint. The aim of this study is to examine the effects of strength training on the torque of the ankle joint for a Down syndrome.
In rat adipocytes, insulin-induced GLUT4 recruitment to the plasma membrane (PM) is associated with characteristic changes in the GLUT4 contents of three distinct endosomal fractions, T, H, and L. The organelle-specific marker distribution pattern suggests that these endosomal GLUT4 compartments are sorting endosomes (SR), GLUT4-storage endosomes (ST), and GLUT4 exocytotic vesicules (EV), respectively, prompting us to analyze GLUT4 recycling based upon a four-compartment kinetic model. Our analysis revealed that insulin modulates GLUT4 trafficking at multiple steps, including not only the endocytotic and exocytotic rates, but also the two rate coefficients coupling the three intracellular compartments. This analysis assumes that GLUT4 cycles through PM T, H,L, and back to PM, in that order, with transitions characterized by four first-order coefficients. Values assigned to these coefficients are based upon the four steady-state GLUT4 pool sizes assessed under both basal and insulin stimulated states and the transition time courses observed in the plasma membrane GLUT4 pool. Here we present the first reported experimental measurements of transient changes in each of the four GLUT4 compartments during the insulin-stimulated to basal transition in rat adipocytes and compare these experimental results with the corresponding model simulations. The close correlation of these results offers clear support for the general validity of the assumed model structure and the assignment of the T compartment to the sorting endosome GLUT4 pool. Variations in the recycling pathway from that of an unbranched cyclic topography are also considered in the light of these experimental observations. The possibility that H is a coupled GLUT4 storage compartment lying outside the direct cyclic pathway is contraindicated by the data. Okadaic acid-induced GLUT4 recruitment is accompanied by modulation of the rate coefficients linking individual endosomal GLUT4 compartments, further demonstrating a significant role of the endosomal pathways in GLUT4 exocytosis.
Cadmium stimulates glucose transport in fibroblasts, apparently by increasing the intrinsic activity of GLUT1 [Harrison, S. A., Buxton, J. M., Clancy, B. M., & Czech, M. P. (1991) J. Biol. Chem. 266, 19438−19449]. In the present study, we examined whether cadmium affects the binding in vitro of purified GLUT1 to glucose and cytochalasin B. Cadmium inhibited cytochalasin B binding to GLUT1 competitively by reducing its binding affinity with an apparent inhibition constant of approximately 0.2 mM. However, d-glucose displaced cytochalasin B bound to GLUT1 as effectively in the presence of cadmium as in its absence, and detailed analysis of this displacement revealed that cadmium in fact increases the substrate binding affinity significantly. These findings suggest that cadmium induces a specific conformational change in GLUT1 that interferes with cytochalasin B binding but enhances substrate binding. This is the first clear demonstration in which the substrate and cytochalasin B binding activities of GLUT1 are differentially affected, which may offer insight into the workings of the glucose transporter.
Kinetics of GLUT4 Recycling in Adipocytes 17711 u,,, = 1735 cm".All compounds were homogeneous on TLC.[3H] B3GL (15 Ci/mmol) was synthesized through Cl-3H exchange carried
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