AJP - Endocrinology and Metabolism, Vol 273, Issue 1 E28-E36, Copyright © 1997 by American Physiological Society
Phorbol esters stimulate muscle glucose transport by a mechanism distinct from the insulin and hypoxia pathways
P. A. Hansen, J. A. Corbett and J. O. Holloszy
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Glucose transport in skeletal muscle can be stimulated by insulin and also
by contractions and hypoxia. Activation of protein kinase C (PKC)
stimulates glucose transport in muscle and other insulin-responsive cells.
This study was performed to determine if the diacylglycerol (DAG)/phorbol
ester-sensitive PKC isoforms participate in insulin and/or
hypoxia-stimulated glucose transport in skeletal muscle. The phorbol ester
12-deoxyphorbol 13-phenylacetate 20-acetate (dPPA) induced a three- to
fourfold increase in glucose transport in rat epitrochlearis muscle. The
effects of dPPA on glucose transport and on cell surface GLUT-4 were
completely additive to the maximal effects of insulin or hypoxia. Phorbol
ester treatment induced 5- to 10-fold increases in phosphorylation of the
myristoylated alanine-rich C kinase substrate protein in muscle, whereas
insulin and hypoxia had negligible effects. Calphostin C, an inhibitor of
DAG-sensitive PKC isoforms, decreased glucose transport stimulation by dPPA
but not by insulin or hypoxia. These results provide evidence that
activation of DAG/phorbol ester-sensitive PKCs is not involved in the
pathways by which either insulin or hypoxia stimulates muscle glucose
transport. They also show that activation of this group of PKCs increases
glucose transport by a mechanism that is independent of and additive to the
effects of insulin or hypoxia.
