Inhibition of monosaccharide transport in the intact rat liver by stevioside.
The transport and metabolism of D-glucose and D-fructose in the isolated perfused rat liver and the influence of stevioside and its derivatives were investigated. The transport parameters were measured by the multiple indicator dilution technique. The maximal exchange rate of D-glucose was 700 mumol X min-1 X ml-1 and the Km was 38 mM. Stevioside and its derivatives (isosteviol and steviolbioside) inhibited D-glucose and D-fructose transport across the cell membrane. The half-maximal effect at 1 mM D-glucose occurred at 0.8 mM stevioside. The inhibitory action of stevioside was of mixed type. Isosteviol was more potent than stevioside (half-maximal effect at 0.4 mM), whereas steviolbioside was less active (50% inhibition at 2.5 mM). Stevioside was without effect on D-glucose metabolism, except for transient changes in D-glucose release, reflecting changes in the intracellular concentration. D-Fructose consumption, however, was specifically affected (half-maximal effect at 2.8 mM), as well as all parameters depending on D-fructose transformation (D-glucose production, L-lactate and pyruvate production, and extra oxygen uptake). In livers releasing D-glucose from endogenous glycogen, strong inhibition of transport increased the intracellular to extracellular D-glucose concentration ratio (Ci/Ce). The control values of Ci/Ce, representing an average over the total intracellular water space, were always smaller than unity. The latter observation may indicate that D-glucose does not have access to the whole intracellular water space.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002250:Carbon Radioisotopes; D004224:Diterpenes; D045786:Diterpenes, Kaurane; D005632:Fructose / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D005960:Glucosides / Q000494:pharmacology*; D006027:Glycosides / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010710:Phosphates / Q000378:metabolism; D010761:Phosphorus Radioisotopes; D051381:Rats; D011919:Rats, Inbred Strains; D013395:Sucrose / Q000378:metabolism; D013549:Sweetening Agents / Q000494:pharmacology*; D013729:Terpenes / Q000494:pharmacology*; D014316:Tritium
D002250:Carbon Radioisotopes; D004224:Diterpenes; D045786:Diterpenes, Kaurane; D005960:Glucosides; D006027:Glycosides; D010710:Phosphates; D010761:Phosphorus Radioisotopes; D013549:Sweetening Agents; D013729:Terpenes; C012043:stevioside; D014316:Tritium; D005632:Fructose; D013395:Sucrose; D005947:Glucose