The long term objective of my research is to elucidate the mechanism of insulin actions at the molecular level.
The specific aims of the proposed studies are:
(Aim 1) to substantiate further the translocation hypothesis of insulin action on glucose transport, (Aim 2) to characterize the action of insulin on the K/m value of hexose transport, (Aim 3) to determine why certain characteristics of glucose transport in muscle are different from those in adipocytes, (Aim 4) to explore the possible mechanisms of insulin actions in muscle and adipocytes, and (Aim 5) to elucidate the mechanisms of insulin action of cAMP phosphodiesterase. To achieve Aim I, I will (a) track the movement of labeled glucose transporter in isolated rat epididymal and perirenal adipocytes, (b) study the effects of insulin on the V/max values for the transport of several sugar isomersin adipocytes, and (c) reevaluate the data that are apparently in disagreement with the translocation hypothesis. To achieve Aim 2, I will (a) reexamine the K/m value of glucose transport in the reconstitute liposome system, (b) characterize the insulin effect of the K/m value of hexose transport in adipocytes, and (c) to examine whether insulin changes the K/m value of glucose transport in hepatocytes. To achieve Aim 3, I will study how the V/max and K/m values of glucose transport in freshly isolated cardiac myocytes are affected by TPA (a phorbal ester), insulin, anoxia, and the agents that mimic the action of insulin in adipocytes. To achieve Aim 4, I will (a) study the effect of a low concentration of Ca2+ using A- 23187 and Quin 2/AM in two separate experiments, and (b) examine the relative effects of Mn2+ on the receptor kinase and glucose transport activities. To achieve Aim 5, I will study (a) factors involved in the stimulation of phosphodiesterase in the cell, (b) the reversal of insulin effect on phosphodiesterase, and (c) attempt to activate the enzyme in a cell-free system with cAMP-dependent protein kinase.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK019925-11
Application #
3226596
Study Section
Metabolism Study Section (MET)
Project Start
1977-04-01
Project End
1992-08-31
Budget Start
1987-09-01
Budget End
1988-08-31
Support Year
11
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37203
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