Glifloziny patří mezi velmi perspektivní antidiabetika a kardiovaskulární léky. Jejich mechanismus účinku spočívá v inhibici transportního systému, který zajišťuje kotransport sodíku a glukózy (SGLT) a je exprimován v tenkém střevě (SGLT1), proximálním tubulu (SGLT2), ale i v jiných tkáních. Selektivita účinku vůči SGLT1 a SGLT2 je nejvýznamnějším faktorem ovlivňujícím farmakodynamické účinky gliflozinů. Článek je prvním v řadě textů, které dále popíší metabolismus a transport gliflozinů, míru a cesty jejich glukuronizace a lékové interakce.
Gliflozins are among the most promising antidiabetics and cardiovascular drugs. Their mechanism of action is the inhibition of sodium-glucose co-transporter (SGLT), which is expressed in the small intestine (SGLT1), the proximal tubule (SGLT2), and other tissues. The selectivity of action against SGLT1 and SGLT2 is the most important factor influencing the pharmacodynamic effects of gliflozins. The article is the first in a series of articles that further describe the metabolism and transport of gliflozins, the extent and pathways of their glucuronidation, and the drug interactions of gliflozins.
Lipid bilayer properties are quantified with a variety of arbitrary selected parameters such as molecular packing and dynamics, electrostatic potentials or permeability. In the paper we determined the effect of phloretin and 6-ketocholestanol (dipole potential modifying agents) on the membrane hydration and efficiency of the trans-membrane water flow. The dynamics of water molecules within the lipid bilayer interface was evaluated using solvent relaxation method, whereas the osmotically induced trans-membrane water flux was estimated with the stopped-flow method using the liposome shrinkage kinetics. The presence of phloretin or 6-ketocholestanol resulted in a change of both, the interfacial hydration level and osmotically driven water fluxes. Specifically, the presence of 6-ketocholestanol reduced the amount and mobility of water in the membrane interface. It also slows the osmotically induced water flow. The interfacial hydration change caused by phloretin was much smaller and the effect on osmotically induced water flow was opposite to that of 6-ketocholestanol.
- MeSH
- floretin chemie MeSH
- fluorescenční barviva chemie MeSH
- ketocholesteroly chemie MeSH
- lipidové dvojvrstvy chemie metabolismus MeSH
- liposomy chemie metabolismus MeSH
- permeabilita MeSH
- simulace molekulární dynamiky * MeSH
- voda chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- floretin farmakologie MeSH
- hodnoty glomerulární filtrace MeSH
- karbonylkyanid-m-chlorfenylhydrazon farmakologie MeSH
- krysa rodu rattus MeSH
- ledviny fyziologie účinky léků MeSH
- močovina moč MeSH
- oxidativní fosforylace účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
