Insulin action will be studied in terms of 4 interrelated areas including 1) the isolation, purification to homogeneity and structure determination of several novel mediators of insulin action; 2) the separate high affinity binding and bioactivity domains of the insulin molecule; 3) the mechanism of the enhanced insulin receptor phosphorylation in the presence of the hormone and its possible relationship to mediator formation and 4) studies on the biochemical mechanism(s) of insulin resistance in human cells of diabetic patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
2R01AM014334-17
Application #
3150906
Study Section
Metabolism Study Section (MET)
Project Start
1975-05-01
Project End
1986-04-30
Budget Start
1985-09-25
Budget End
1986-04-30
Support Year
17
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Virginia
Department
Type
Schools of Medicine
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Paule, C R; Larner, J (1996) Characterization of a nucleotide stimulated aspartic proteinase in rat liver plasma membranes. J Basic Clin Physiol Pharmacol 7:121-36
Galasko, G T; Abe, S; Lilley, K et al. (1996) Circulating factors and insulin resistance. II. The action of the novel myo-inositol cyclic 1,2-inositol phosphate phosphoglycan insulin antagonist from human plasma in regulating pyruvate dehydrogenase phosphatase. J Clin Endocrinol Metab 81:1051-7
Galasko, G T; Bao, Y; Broomfield, S J et al. (1995) Circulating factors and insulin resistance. I. A novel myoinositol 1,2-cyclic phosphate phosphoglycan insulin antagonist from human plasma is elevated in noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 80:2419-29
Romero, G; Gamez, G; Huang, L C et al. (1990) Anti-inositolglycan antibodies selectively block some of the actions of insulin in intact BC3H1 cells. Proc Natl Acad Sci U S A 87:1476-80
Larner, J; Huang, L C; Suzuki, S et al. (1989) Insulin mediators and the control of pyruvate dehydrogenase complex. Ann N Y Acad Sci 573:297-305
Romero, G; Luttrell, L; Rogol, A et al. (1988) Phosphatidylinositol-glycan anchors of membrane proteins: potential precursors of insulin mediators. Science 240:509-11
Messina, J L; Hamlin, J; Larner, J (1987) Insulin-mimetic actions of wheat germ agglutinin and concanavalin A on specific mRNA levels. Arch Biochem Biophys 254:110-5
Malchoff, C D; Huang, L; Gillespie, N et al. (1987) A putative mediator of insulin action which inhibits adenylate cyclase and adenosine 3',5'-monophosphate-dependent protein kinase: partial purification from rat liver: site and kinetic mechanism of action. Endocrinology 120:1327-37
Leef, J W; Larner, J (1987) Insulin-mimetic effect of trypsin on the insulin receptor tyrosine kinase in intact adipocytes. J Biol Chem 262:14837-42
Suzuki, S; Toyota, T; Tamura, S et al. (1987) ATP-Mn2+ stimulates the generation of a putative mediator of insulin action. J Biol Chem 262:3199-204

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