Abstract

The long-term objective of this research is to explain the mechanism of insulin action at the molecular level. The specific objective of the proposed study is to test and substantiate the working hypothesis recently proposed from this laboratory as well as from Cushman's laboratory at NIH. According to the hypothesis, insulin stimulates glucose transport in fat cells by promoting translocation of the glucose transport activity to the plasma membrane from an intracellular storage site. In the proposed study, we will measure the glucose transport activity in a cell-free liposome system reconstituted with the glucose transport activities solubilized from the plasma membrane-rich fraction and Golgi-rich fraction. The translocation hypothesis predicts that insulin changes the two transport activities to the same extent towards opposite directions. However, the apparent effect of insulin currently observed in the Golgi-rich fraction is larger than that in the plasma membrane fraction. Therefore, we plan to investigate the reason for this paradoxical observation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK019925-10
Application #
3226598
Study Section
Metabolism Study Section (MET)
Project Start
1977-04-01
Project End
1987-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
10
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Vanderbilt University Medical Center
Department
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37203

  Publications

Seo, S B; McNamara, P; Heo, S et al. (2001) Regulation of histone acetylation and transcription by INHAT, a human cellular complex containing the set oncoprotein. Cell 104:119-30
Printz, R L; Osawa, H; Ardehali, H et al. (1997) Hexokinase II gene: structure, regulation and promoter organization. Biochem Soc Trans 25:107-12
Ardehali, H; Yano, Y; Printz, R L et al. (1996) Functional organization of mammalian hexokinase II. Retention of catalytic and regulatory functions in both the NH2- and COOH-terminal halves. J Biol Chem 271:1849-52
Makino, H; Manganiello, V C; Kono, T (1994) Roles of ATP in insulin actions. Annu Rev Physiol 56:273-95
Yano, Y; Sumida, Y; Benzing, C F et al. (1993) Primary sites of actions of staurosporine and H-7 in the cascade of insulin action to glucose transport in rat adipocytes. Biochim Biophys Acta 1176:327-32
Yano, Y; May, J M (1993) Ligand-induced conformational changes modify proteolytic cleavage of the adipocyte insulin-sensitive glucose transporter. Biochem J 295 ( Pt 1):183-8
Goto, Y; Sumida, Y; Flanagan, J E et al. (1992) Effects of fluorescein isothiocyanate on insulin actions in rat adipocytes. Arch Biochem Biophys 293:224-30
Shibata, H; Robinson, F W; Benzing, C F et al. (1991) Evidence that protein kinase C may not be involved in the insulin action on cAMP phosphodiesterase: studies with electroporated rat adipocytes that were highly responsive to insulin. Arch Biochem Biophys 285:97-104
Shibata, H; Robinson, F W; Soderling, T R et al. (1991) Effects of okadaic acid on insulin-sensitive cAMP phosphodiesterase in rat adipocytes. Evidence that insulin may stimulate the enzyme by phosphorylation. J Biol Chem 266:17948-53
Shibata, H; Kono, T (1990) Cell-free stimulation of the insulin-sensitive cAMP phosphodiesterase by the joint actions of ATP and the soluble fraction from insulin-treated rat liver. Biochem Biophys Res Commun 170:533-9

Showing the most recent 10 out of 13 publications