Current progress from this laboratory has indicated that endotoxin administration impairs hepatic glucose metabolism by two different mechanisms: one by a modification of membrane lipid structure and property and the other by acting through the phosphorylation-dephosphorylation of the enzyme and the receptor proteins. The primary aims of this proposal are to continue our search for the understanding of the pathophysiology of hepatic glucose dyshomeostasis at the molecular level and ultimately to develop a rational remedy for the better management of shock. The specific objectives include studies of the phosphorylation- dephosphorylation of adrenergic receptors and of glycogen synthase and phosphorylase, and their relationships to changes in the receptor dynamics and to glycogen depletion in endotoxin shock; investigation of the kinetics of protein kinase A and protein kinase C and their associations with transmembrane Ca2+ transport and with altered glucose homeostasis in dog liver during shock; studies of phospholipase A activation and its role on Ca2+ uptake by the plasma membrane and the endoplasmic reticulum; studies of the receptor-mediated alterations of phospholipase C, of inositol phospholipid turnover, and of protein kinase C and their relationships with Ca2+ homeostasis in the liver in shock; studies of hepatocyte-liposome interactions; and development of a suitable liposome preparation to be used as a membrane modifier and also as a drug carrier system for the therapeutic intervention of hepatic glucose dyshomeostasis in endotoxin shock.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM031664-07
Application #
3279871
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1982-07-01
Project End
1994-03-31
Budget Start
1991-04-01
Budget End
1992-03-31
Support Year
7
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Saint Louis University
Department
Type
Schools of Medicine
DUNS #
City
Saint Louis
State
MO
Country
United States
Zip Code
63103
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