In fat and muscle, the interaction of insulin with its specific cell-surface receptor results in the rapid stimulation of glucose transport into these tissues. This increased rate of glucose transport is a consequence of an increase in the number of cell surface glucose transport proteins that occurs concomitant with a decrease in intracellular transporters. This proposal is aimed at understanding the biochemical and morphological details that underlie coupling of ligand-receptor interaction to transport activation. It is known that the insulin receptor is a tyrosine-specific protein kinase. The purified insulin receptor will be reconstituted and the structure/function correlates responsible for kinase activity will be studied in detail to potentially gain insight into the signal(s) required for transport activation. Anti-receptor antibodies will be prepared and used to further dissect structure/function relationships for the insulin receptor. In addition, these antibodies will be made electron-dense for the morphological study of receptor dynamics and metabolism. A similar approach will be applied to the study of the insulin-sensitive glucose transport of fat cells. The transporter will be purified and biochemically dissected. Antibodies against it will be prepared as both biochemical and morphological tools. In particular, antibodies that recognize fat cell transporters in situ will be made electron dense in order to identify structure involved in the insulin-affected movement of transporters to and from the cell surface. This proposal encompasses an ambitious multi-faceted approach combining biochemical, immunological and morphological techniques to elucidate the fundamentally important process of insulin-regulated glucose utilization.

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 #
5K04DK001352-04
Application #
3072369
Study Section
Metabolism Study Section (MET)
Project Start
1984-07-01
Project End
1989-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
4
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Boston University
Department
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118