Drug metabolizing enzymes (DMEs) and transporters mediate elimination of
many compounds, although minimal data are available on the regulation
and activity of these mechanisms in humans with 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
will be trained in the use of rtPCR, HPLC or LC-MS/MS to enable him/her
to carry out research independently.