Altered glucose regulation is a key feature of metabolic dysfunction in sepsis and shock. Previous studies by the investigator and others have shown that altered hepatic receptor signaling plays an important role in hepatic glucose metabolic dysfunction in shock. The primary goal of the proposed research is to investigate molecular mechanisms responsible for changes in the adrenergic G protein effector pathways in rat liver during the early """"""""hypermetabolic"""""""" and late """"""""hypometabolic"""""""" phases of sepsis. The specific objectives include: 1) studies of transcriptional and translational mechanisms for the externalization and internalization of adrenergic receptors in rat liver during the early and late phase of sepsis; 2) characterization of the transcriptional and translational modifications of Gas, Gai, Gq, and the B subunit of the G proteins in rat livers in the two septic phases;and 3) the investigation of responses mediated by the G proteins (Gas, Gai, Gq and the B units), i.e., activities of the enzymes, adenylate cyclase, phospholipase C, D, and A2 and their relationships to its activation during early and late sepsis.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM031664-12
Application #
2444543
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1982-07-01
Project End
1999-06-30
Budget Start
1997-07-01
Budget End
1998-06-30
Support Year
12
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Saint Louis University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
City
Saint Louis
State
MO
Country
United States
Zip Code
63103
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Dong, L W; Yang, J; Tong, L J et al. (1999) Transcriptional regulation of alpha1-adrenoceptor gene in the rat liver during different phases of sepsis. Biochim Biophys Acta 1453:207-15

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