Reduced glucose-6-phosphorylase and NADPH generating enzyme activities associated with glibenclamide induced hypoglycemia and hypoinsulinemia in genetically obese mice

Characterization of transgenic mouse strains using six human hepatic cytochrome P450 probe substrates

“…The use of transgenic mouse models has also increased to the point where many early pharmacology tests of efficacy occur in a mouse model of the disease under study. Perhaps the most widely studied transgenic mouse strains from the point of view of drug-metabolizing enzymes are oh/ob and db/db (Rouer and Leroux 1980, Stengard et al 1987, Karvonen et al 1990, Roe et al 1999, Watson et al 1999. More recently, the mdr la ( -/ -) mouse has become a useful tool in understanding drug transport mediated by P-glycoprotein (Schuetz et al 1998) as well as in defining its relationship with CYP3A4 (Schuetz et al 1996).…”

“…While in vitro systems now play a major role in the determination of xenobiotic metabolism (Ekins et al 1999), in vivo models, such as the transgenic mouse, are increasingly being evaluated with the hope of predicting human responses in vivo. The transgenic mouse is being widely used as surrogate models for disease states such as obesity (Karvonen et al 1990, Roe et al 1999, Watson et al 1999, diabetes mellitus (Knodell et al 1984) and fulminant hepatitis (Chemin et al 1996). The transgenic mouse has also been widely used as a pharmacological tool for the study of growth hormone effects (Cheriathundam et al 1998), drug transport (Schuetz et al 1996, Perloff e« al.…”

“…The ob/oh mouse is probably the most extensively studied transgenic mouse in this regard (Rouer and Leroux 1980, Stengard et al 1987, Karvonen et al 1990, Roe et al 1999, Watson et al 1999) as it has been characterized for CYPl A, CYP2B, CYP2E, CYP3A and CYP4A activities. The data obtained for this strain have been variable, especially with regard to CYP2E activity (Roe et al 1999, Watson et al 1999.…”