PMID- 17097148
OWN - NLM
STAT- MEDLINE
DCOM- 20070315
LR  - 20220318
IS  - 0163-7258 (Print)
IS  - 0163-7258 (Linking)
VI  - 113
IP  - 1
DP  - 2007 Jan
TI  - The role of intracellular signaling in insulin-mediated regulation of drug 
      metabolizing enzyme gene and protein expression.
PG  - 88-120
AB  - Endogenous factors, including hormones, growth factors and cytokines, play an 
      important role in the regulation of hepatic drug metabolizing enzyme expression 
      in both physiological and pathophysiological conditions. Diabetes, fasting, 
      obesity, protein-calorie malnutrition and long-term alcohol consumption produce 
      changes in hepatic drug metabolizing enzyme gene and protein expression. This 
      difference in expression alters the metabolism of xenobiotics, including 
      procarcinogens, carcinogens, toxicants and therapeutic agents, potentially 
      impacting the efficacy and safety of therapeutic agents, and/or resulting in 
      drug-drug interactions. Although the mechanisms by which xenobiotics regulate 
      drug metabolizing enzymes have been studied intensively, less is known regarding 
      the cellular signaling pathways and components which regulate drug metabolizing 
      enzyme gene and protein expression in response to hormones and cytokines. Recent 
      findings, however, have revealed that several cellular signaling pathways are 
      involved in hormone- and growth factor-mediated regulation of drug metabolizing 
      enzymes. Our laboratory has reported that insulin and growth factors regulate 
      drug metabolizing enzyme gene and protein expression, including cytochromes P450 
      (CYP), glutathione S-transferases (GST) and microsomal epoxide hydrolase (mEH), 
      through receptors which are members of the large receptor tyrosine kinase (RTK) 
      family, and by downstream effectors such as phosphatidylinositol 3-kinase, 
      mitogen activated protein kinase (MAPK), Akt/protein kinase B (PKB), mammalian 
      target of rapamycin (mTOR), and the p70 ribosomal protein S6 kinase (p70S6 
      kinase). Here, we review current knowledge of the signaling pathways implicated 
      in regulation of drug metabolizing enzyme gene and protein expression in response 
      to insulin and growth factors, with the goal of increasing our understanding of 
      how disease affects these signaling pathways, components, and ultimately gene 
      expression and translational control.
FAU - Kim, Sang K
AU  - Kim SK
AD  - Institute of Environmental Health Sciences, Wayne State University, 2727 Second 
      Avenue, Room 4000, Detroit, MI 48201, USA.
FAU - Novak, Raymond F
AU  - Novak RF
LA  - eng
GR  - R01 ES003656/ES/NIEHS NIH HHS/United States
GR  - P30 ES006639-13/ES/NIEHS NIH HHS/United States
GR  - R01 ES003656-17/ES/NIEHS NIH HHS/United States
GR  - P30 ES06639/ES/NIEHS NIH HHS/United States
GR  - ES03656/ES/NIEHS NIH HHS/United States
GR  - P30 ES006639/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20061113
PL  - England
TA  - Pharmacol Ther
JT  - Pharmacology & therapeutics
JID - 7905840
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Isoenzymes)
RN  - 0 (Receptors, Growth Factor)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - EC 2.5.1.18 (Glutathione Transferase)
RN  - EC 2.7.10.1 (Receptor, Insulin)
RN  - EC 3.1.3.2 (Phosphoric Monoester Hydrolases)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
RN  - EC 6.3.2.2 (Glutamate-Cysteine Ligase)
SB  - IM
MH  - Animals
MH  - Cytochrome P-450 Enzyme System/biosynthesis/genetics
MH  - Epoxide Hydrolases/biosynthesis/genetics
MH  - *Gene Expression Regulation, Enzymologic/drug effects
MH  - Glutamate-Cysteine Ligase/biosynthesis/genetics
MH  - Glutathione Transferase/biosynthesis/genetics
MH  - Humans
MH  - Hypoglycemic Agents/*metabolism/pharmacology
MH  - Insulin/*metabolism/pharmacology
MH  - Intercellular Signaling Peptides and Proteins/metabolism
MH  - Isoenzymes
MH  - Liver/drug effects/*enzymology
MH  - MAP Kinase Signaling System/drug effects
MH  - Metabolic Detoxication, Phase II/genetics
MH  - Phosphoric Monoester Hydrolases/metabolism
MH  - Receptor, Insulin/metabolism
MH  - Receptors, Growth Factor/metabolism
MH  - *Signal Transduction/drug effects
PMC - PMC1828071
MID - NIHMS16392
EDAT- 2006/11/14 09:00
MHDA- 2007/03/16 09:00
PMCR- 2008/02/01
CRDT- 2006/11/14 09:00
PHST- 2006/07/11 00:00 [received]
PHST- 2006/07/18 00:00 [accepted]
PHST- 2006/11/14 09:00 [pubmed]
PHST- 2007/03/16 09:00 [medline]
PHST- 2006/11/14 09:00 [entrez]
PHST- 2008/02/01 00:00 [pmc-release]
AID - S0163-7258(06)00135-5 [pii]
AID - 10.1016/j.pharmthera.2006.07.004 [doi]
PST - ppublish
SO  - Pharmacol Ther. 2007 Jan;113(1):88-120. doi: 10.1016/j.pharmthera.2006.07.004. 
      Epub 2006 Nov 13.