Diabetes and regulation of hepatic drug
metabolism enzymes
Drug metabolizing enzymes (DMEs) and transporters mediate detoxification
and elimination of a wide range of compounds, although minimal data are
available on the regulation and activity of these mechanisms in humans
with type 1 or type 2 diabetes mellitus. Recently, we have observed
significantly higher concentrations of the cholesterol lowering agent,
atorvastatin (ATV) lactones in patients with diabetes mellitus.
Furthermore, in the livers of diabetic donors, we have shown significant
downregulation of cytochrome P450 3A4 (CYP3A4) that is responsible for
the biotransformation of approximately 55% of all marketed medications.
The broad long-term objective of this project is to improve
pharmacotherapy in patients with diabetes mellitus. The central
hypothesis is that diabetes and associated conditions differentially
regulate DMEs and transport mechanisms, thus, resulting in the altered
clearance of xenobiotics including ATV. The student w ill be trained in
the use of rtPCR and HPLC to enable him/her to carry out research
independently.
