The working hypothesis to be tested is that phospholipases C and A2 have a major role in initiating and regulating insulin secretion. According to the hypothesis, glucose is recognized at the plasma membrane by a protein that would then be coupled to phospholipase C. The identity of this protein is unknown but possible candidates include the glucose transporter, a putative glucose receptor, or an enzyme of glycolysis.
Aim #1 is to define the molecular mechanism whereby glucose and other secretagogues activate phospholipase C in insulin secretion.
Aim#2 is to determine whether novel inositol phospholipids (PIP3) are present in islets and insulin-secreting cells, and whether they have a role in insulin secretion.
Aim #3 will define and characterize the role of phospholipase A2 and arachidonic acid accumulation in insulin secretion. Preliminary data show that the muscarinic agonist carbachol stimulates phospholipase A2 and glucose may activate diacylglycerol (DAG) lipase and arachidonate may affect voltage- dependent Ca++ influx.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Modified Research Career Development Award (K04)
Project #
5K04DK002217-05
Application #
2634159
Study Section
Endocrinology Study Section (END)
Program Officer
Hyde, James F
Project Start
1994-01-01
Project End
1998-12-31
Budget Start
1998-01-01
Budget End
1998-12-31
Support Year
5
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Pathology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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Major, C; Wolf, B A (1994) Quantitation of the fatty acid composition of phosphatidic acid by capillary gas chromatography electron-capture detection with picomole sensitivity. J Chromatogr B Biomed Appl 658:233-40

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