Type 2 diabetes mellitus seriously impacts on the quality of life and longevity of millions of Americans. Type 2 diabetes mellitus is caused primarily by impaired signaling by insulin. PI-3- kinase plays a crucial role in the insulin signaling pathway. This research project will better define the mechanism by which PI-3-kinase transduces the insulin signal. Preliminary evidence indicates that insulin stimulates the translocation of PI3K to discrete intracellular locations, quite distinct from the response to other growth factors. It is hypothesized that this distinct subcellular localization is partly responsible for the unique signaling effects of insulin. This will be investigated further by defining the subcellular localization of insulin-stimulated PI-3-kinase signaling, the mechanism governing this localization, and the function of this localization. It is expected that a better understanding of the signaling pathway utilized by insulin will provide insight into the pathophysiology of diabetes mellitus and identify potential targets for novel therapeutics. This project will also contribute significantly to the career development of Dr. Field. Under the mentorship of Dr. Lewis Cantley and Dr. Anne Klibanski this career development award is expected to foster Dr. Field's development into a successful independent clinician-scientist.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08DK065108-04
Application #
6921934
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Hyde, James F
Project Start
2003-09-30
Project End
2008-08-31
Budget Start
2005-09-01
Budget End
2006-08-31
Support Year
4
Fiscal Year
2005
Total Cost
$122,850
Indirect Cost
Name
University of California San Diego
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Dippold, Holly C; Ng, Michelle M; Farber-Katz, Suzette E et al. (2009) GOLPH3 bridges phosphatidylinositol-4- phosphate and actomyosin to stretch and shape the Golgi to promote budding. Cell 139:337-51
Luo, Ji; Field, Seth J; Lee, Jennifer Y et al. (2005) The p85 regulatory subunit of phosphoinositide 3-kinase down-regulates IRS-1 signaling via the formation of a sequestration complex. J Cell Biol 170:455-64
Field, Seth J; Madson, Nikki; Kerr, Monica L et al. (2005) PtdIns(4,5)P2 functions at the cleavage furrow during cytokinesis. Curr Biol 15:1407-12