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Query: UMLS:C0235394 (wasting)
 8,040 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study examined the effects of prolonged hyperglycemia on renal handling of glucose and explored the in vivo pharmacological effects of phlorizin on glucose transport in the rainbow trout. The transport of glucose was examined by experimentally elevating the rate of renal glucose reabsorption via infusion of the fish with exogenous glucose at a rate of 70 micromol kg(-1) h(-1) and by inactivating the glucose transporters via the simultaneous administration of phlorizin (1 micromol kg(-1) h(-1)). Glucose was reabsorbed against a concentration gradient, until plasma glucose levels reached approximately 22 micromol l(-1) and the transport maximum of glucose in the kidney (approximately 145 micromol kg(-1) h(-1)) was exceeded. At this point, glucose was lost to the urine, resulting in glucosuria. Glucosuria affected water reabsorption, approximately doubling the water clearance ratio, and resulted in osmotic diuresis. This in turn reduced Na+ reabsorption, increasing the amount lost to the urine from 0.5% to 2% of the filtered load. Glucose reabsorption was found to be correlated with Na+ reabsorption, though the latter was almost 10-fold higher than glucose transport rates. Phlorizin treatment reduced glucose reabsorption, although it did not block it entirely until 48-72 h of infusion. The glucosuria resulting from the blockade of the glucose transporters resulted in a similar osmotic diuresis and a greater Na+ loss to the urine (9% of filtered load). The results are discussed with respect to the net renal ;wasting' of glucose and the detrimental osmoregulatory and ionoregulatory effects associated with glucosuria caused by carbohydrate-rich diets.
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PMID:Renal regulation of plasma glucose in the freshwater rainbow trout. 1600 May 42

Dapagliflozin (BMS-512148), a specific inhibitor of the sodium-glucose cotransporter SGLT2, is under development by AstraZeneca plc and Bristol-Myers Squibb Co for the potential oral treatment of type 2 diabetes mellitus (T2DM); a fixed-dose combination of dapagliflozin and metformin is also being developed by the companies for the potential treatment of diabetes mellitus. Phlorizin, a naturally occurring O-glucoside, inhibits renal glucose transport and induces glucosuria in rodent models of diabetes; however, phlorizin inhibits other glucose transporters in addition to SGLT2 and thus is not suitable for oral administration. The chemical synthesis of more specific SGLT2 inhibitors led to the identification of dapagliflozin, a C-aryl glucoside that was highly selective for SGLT2 compared with SGLT1. In phase II clinical trials in patients with T2DM, once-daily dapagliflozin induced dose-dependent increases in glucosuria and efficiently reduced HbA1c, fasting and postprandial glucose levels. Dapagliflozin was not associated with significant hypoglycemic episodes or weight gain; rather, the caloric losses related to renal glucose wasting induced a net weight loss. In addition, the diuretic effect observed with dapagliflozin may help to control hypertension, an associated finding in patients with T2DM. The major adverse effect associated with dapagliflozin appears to be an increased occurrence of mycotic genital infections.
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PMID:Dapagliflozin, an oral sodium glucose cotransporter type 2 inhibitor for the treatment of type 2 diabetes mellitus. 1994 22