Inhibition of glucose transport

T3-L1 Mouse embryo fibroblasts Adipocytes TCDD Inhibition of glucose transport and lipoprotein lipase... 

Murphy, W. A. Lumsden, R. D. (1984a). Phloretin inhibition of glucose transport by the tapeworm Hymenolepis diminuta a kinetic analysis. Comparative Biochemistry and Physiology, 78A 749-54. 

Figure 4.17 Schematic of pulsating drug delivery device based on feedback inhibition of glucose transport to glucose oxidase through a hydrogel membrane. Changes in permeability to glucose are accompanied by modulation of drug permeability. Reprinted from [97] with permission from American Institute of Physics.

Other effects of iodide include the inhibition of glucose transport, presumably by reduction of the number of available glucose carriers in pig cells (Filetti et al, 1986), and the inhibition of amino acid and uridine uptake Kleiman de Pisarev et al., 1978 Pisarev and Itoiz, 1972). The relationship of these effects to the previously described effects is not known. 

Griffin JF, Rampal AL, Jung CY (1982) Inhibition of Glucose Transport in Human Erythrocytes by Cytochalasin a Model Based on Diffraction Studies. Proc Natl Acad Sci USA 79 3759... 

Although cytochalasin B normally functions as a reversible inhibitor of glucose transport, upon exposure to ultraviolet light a small proportion of the bound cytochalasin B molecules become covalently linked to the transporter protein [128-130]. Photolabelling is inhibitable by D-glucose and other transported sugars but not by... 

Depletion of ATP is caused by many toxic compounds, and this will result in a variety of biochemical changes. Although there are many ways for toxic compounds to cause a depletion of ATP in the cell, interference with mitochondrial oxidative phosphorylation is perhaps the most common. Thus, compounds, such as 2,4-dinitrophenol, which uncouple the production of ATP from the electron transport chain, will cause such an effect, but will also cause inhibition of electron transport or depletion of NADH. Excessive use of ATP or sequestration are other mechanisms, the latter being more fully described in relation to ethionine toxicity in chapter 7. Also, DNA damage, which causes the activation of poly(ADP-ribose) polymerase (PARP), may lead to ATP depletion (see below). A lack of ATP in the cell means that active transport into, out of, and within the cell is compromised or halted, with the result that the concentration of ions such as Na+, K+, and Ca2+ in particular compartments will change. Also, various synthetic biochemical processes such as protein synthesis, gluconeogenesis, and lipid synthesis will tend to be decreased. At the tissue level, this may mean that hepatocytes do not produce bile efficiently and proximal tubules do not actively reabsorb essential amino acids and glucose. 

Physical or chemical modification of a substrate may additionally selectively affect transformation or uptake Keil and Kirchman (1992) compared the degradation of Rubisco uniformly labeled with 3H amino acids produced via in vitro translation to Rubisco that was reductively methylated with 3H-methane. Although both Rubisco preparations were hydrolyzed to lower molecular weights at approximately the same rate, little of the methylated protein was assimilated or respired. The presence of one substrate may also inhibit uptake of another, as has been demonstrated for anaerobic rumen bacteria. Transport and metabolism of the monosaccharides xylose and arabinose were strongly reduced in Ruminococcus albus in the presence of cellobiose (a disaccharide of glucose), likely because of repression of pentose utilization in the presence of the disaccharide. Glucose, in contrast, competitively inhibited xylose transport and showed noncompetitive inhibition of arabinose transport, likely because of inactivation of arabinose permease (Thurston et al., 1994). 

Risperidone was a fairly potent inhibitor of glucose transport but was not very toxic for cells [in their tests] and olanzapine, a modest inhibitor of glucose transport, actually stimulated proliferation of neuronal cells. Haloperidol was toxic for [experimental cells], however, it did not affect glucose transport. On the other hand, this drug inhibited mitochondrial function (energy metabolism), which may explain its toxicity. 

Cephalosporins are broad-spectrum antibiotics similar in structure to penicillin. For several cephalosporins, therapy is limited by the development of nephrotoxicity. Cephaloridine-induced nephrotoxicity has been examined extensively in laboratory animals and is characterized by an increase in blood urea nitrogen concentration within 24-48 hr, reductions in PAFI and TEA transport, and inhibition of glucose production following treatment. 

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