Kidney glucose uptake

The complex thioamide lolrestat (8) is an inhibitor of aldose reductase. This enzyme catalyzes the reduction of glucose to sorbitol. The enzyme is not very active, but in diabetic individuals where blood glucose levels can. spike to quite high levels in tissues where insulin is not required for glucose uptake (nerve, kidney, retina and lens) sorbitol is formed by the action of aldose reductase and contributes to diabetic complications very prominent among which are eye problems (diabetic retinopathy). Tolrestat is intended for oral administration to prevent this. One of its syntheses proceeds by conversion of 6-methoxy-5-(trifluoroniethyl)naphthalene-l-carboxyl-ic acid (6) to its acid chloride followed by carboxamide formation (7) with methyl N-methyl sarcosinate. Reaction of amide 7 with phosphorous pentasulfide produces the methyl ester thioamide which, on treatment with KOH, hydrolyzes to tolrestat (8) 2[. 

GLUT 2 Liver, pancreatic B cell, small intestine, kidney Rapid uptake and release of glucose... 

GLUTS Brain, kidney, placenta Uptake of glucose... 

Sodium SGLTl -dependent unidirectionai transporter Small intestine and kidney Active uptake of glucose from lumen of intestine and reabsorption of glucose in proximal tubule of kidney against a concentration gradient... 

The uptake of glucose by brain, liver, kidneys, erythrocytes, and the islets of Langerhans is unaffected by insulin. However, in muscle and adipose tissues insulin stimulates glucose uptake. Part of this effect results from insulin-induced translocation of molecules of the 509-residue glucose transport protein GLUT4 (Chapter 8) from the cytosol into the plasma membrane where it can function.354-3563 Insulin apparently also increases the rate of synthesis of the transporters. 

In primary rahhit proximal tuhular (RPT) cells cisplatin exposure resulted in an inhihition of DNA synthesis, which is most likely related to the primary anti-tumorigenic mechanism of this compound i.e. DNA inter and intra strand cross linking [117]. RNA and protein synthesis were decreased in RPT cells and quiescent LLC-PK cells upon cisplatin exposure [117, 118]. Other effects of cisplatin on cultured RPT include a decrease in glucose uptake, an inhihition of Na -K ATPase and alterations in total glutathione content [117]. In the normal rat kidney (NRK) cell hne cisplatin (IpM for 48h) induced a marked increase in the level of lipid peroxides [119]. 

Fig. 12. Overshoot in glucose-uptake by vesicles. o-Glucose uptake by brush-border vesicles from kidney and intestine under different ion gradients. (From [100].)...

Figure 8.29 The initial reactions of glutamine metabolism in kidney, intestine and cells of the immune system. The initial reaction in all these tissues is the same, glutamine conversion to glutamate catalysed by glutaminase the next reactions are different depending on the function of the tissue or organ. In the kidney, glutamate dehydrogenase produces ammonia to buffer protons. In the intestine, the transamination produces alanine for release and then uptake and formation of glucose in the liver. In the immune cells, transamination produces aspartate which is essential for synthesis of pyrimidine nucleotides required for DNA synthesis otherwise it is released into the blood to be removed by the enterocytes in the small intestine or by cells in the liver.

Some cells couple the pure transport forms discussed on p. 218—i.e., passive transport (1) and active transport (2)—and use this mechanism to take up metabolites. In secondary active transport (3), which is used for example by epithelial cells in the small intestine and kidney to take up glucose and amino acids, there is a symport (S) located on the luminal side of the membrane, which takes up the metabolite M together with an Na" ion. An ATP-dependent Na transporter (Na /lC ATPase see p. 350) on the other side keeps the intracellular Na+ concentration low and thus indirectly drives the uptake of M. Finally, a uniport (U) releases M into the blood. 

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