Faculty Collaboration Database

Phorbol esters stimulate muscle glucose transport by a mechanism distinct from the insulin and hypoxia pathways. Am J Physiol 1997 Jul;273(1 Pt 1):E28-36

Date

07/01/1997

Pubmed ID

9252476

DOI

10.1152/ajpendo.1997.273.1.E28

Scopus ID

2-s2.0-0030858852 (requires institutional sign-in at Scopus site)   40 Citations

Abstract

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.

Author List

Hansen PA, Corbett JA, Holloszy JO

Author

John A. Corbett PhD Chair, Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Biological Transport
Enzyme Activation
Enzyme Inhibitors
Glucose
Glucose Transporter Type 4
Hypoxia
Intracellular Signaling Peptides and Proteins
Inulin
Isoenzymes
Kinetics
Male
Membrane Proteins
Monosaccharide Transport Proteins
Muscle Contraction
Muscle Proteins
Muscle, Skeletal
Myristoylated Alanine-Rich C Kinase Substrate
Naphthalenes
Phorbol Esters
Protein Kinase C
Proteins
Rats
Rats, Wistar
Tetradecanoylphorbol Acetate