AJP - Heart Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol 276: H1520-H1526, 1999;
0363-6135/99 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by de Luca, J. P.
Right arrow Articles by Miller, T. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by de Luca, J. P.
Right arrow Articles by Miller, T. B., Jr.
Vol. 276, Issue 5, H1520-H1526, May 1999

Wortmannin inhibits insulin-stimulated activation of protein phosphatase 1 in rat cardiomyocytes

Jane P. de Luca1, Alice K. Garnache2, Jill Rulfs1, and Thomas B. Miller Jr.2

1 Department of Biology and Biotechnology, Worcester Polytechnic Institute, Worcester, 01609; and 2 Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01655

A major function of insulin in target tissues is the activation of glycogen synthase. Phosphatidylinositol 3-kinase (PI3K) has been implicated in the insulin-induced activation of glycogen synthase, although the true function of this enzyme remains unclear. Data presented here demonstrate that the PI3K inhibitors wortmannin and LY-294002 block the insulin-stimulated activation of protein phosphatase 1 (PP1) in rat ventricular cardiomyocytes. This loss of phosphatase activation mimics that seen in diabetic cardiomyocytes, in which insulin stimulation fails to activate both PP1 and glycogen synthase. Interestingly, in diabetic cells, insulin stimulated PI3K activity to 300% of that in untreated controls, whereas this activity was increased by only 77% in normal cells. PI3K protein levels, however, were similar in normal and diabetic cells. Our results indicate that PI3K is involved in the stimulation of glycogen synthase activity by insulin through the regulation of PP1. The inability of insulin to stimulate phosphatase activity in diabetic cells, despite a significant increase in PI3K activity, suggests a defect in the insulin signaling pathway that contributes to the pathology of insulin-dependent diabetes.

phosphatidylinositol 3-kinase; glycogen synthase; glycogen synthase phosphatase; diabetes; primary culture cells; insulin signaling


This article has been cited by other articles:


Home page
 DiabetesHome page
L. Laviola, G. Belsanti, A. M. Davalli, R. Napoli, S. Perrini, G. C. Weir, R. Giorgino, and F. Giorgino
Effects of Streptozocin Diabetes and Diabetes Treatment by Islet Transplantation on In Vivo Insulin Signaling in Rat Heart
Diabetes, December 1, 2001; 50(12): 2709 - 2720.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y. Katayose, M. Li, S. W. K. Al-Murrani, S. Shenolikar, and Z. Damuni
Protein Phosphatase 2A Inhibitors, I1PP2A and I2PP2A, Associate with and Modify the Substrate Specificity of Protein Phosphatase 1
J. Biol. Chem., March 24, 2000; 275(13): 9209 - 9214.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
T. C. Jensen, S. M. Crosson, P. M. Kartha, and M. J. Brady
Specific Desensitization of Glycogen Synthase Activation by Insulin in 3T3-L1 Adipocytes. CONNECTION BETWEEN ENZYMATIC ACTIVATION AND SUBCELLULAR LOCALIZATION
J. Biol. Chem., December 15, 2000; 275(51): 40148 - 40154.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online