Endothelin-1 impairs glucose transporter trafficking via a membrane-based mechanism

Andrew B. Strawbridge, Jeffrey Elmendorf

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Endothelin-1 (ET-1) disrupts insulin-regulated glucose transporter GLUT4 trafficking. Since the negative consequence of chronic ET-1 exposure appears to be independent of signal disturbance along the insulin receptor substrate-1/phosphatidylinositol (PI) 3-kinase (PI3K)/Akt-2 pathway of insulin action, we tested if ET-1 altered GLUT4 regulation engaged by osmotic shock, a PI3K-independent stimulus that mimics insulin action. Regulation of GLUT4 by hyperosmotic stress was impaired by ET-1. Because of the mutual disruption of both insulin- and hyperosmolarity-stimulated GLUT4 translocation, we tested whether shared signaling and/or key phosphatidylinositol 4,5-bisphosphate (PIP2)-regulated cytoskeletal events of GLUT4 trafficking were targets of ET-1. Both insulin and hyperosmotic stress signaling to Cbl were impaired by ET-1. Also, plasma membrane PIP2 and cortical actin levels were reduced in cells exposed to ET-1. Exogenous PIP2, but not PI 3,4,5-bisphosphate, restored actin structure, Cbl activation, and GLUT4 translocation. These data show that ET-1-induced PIP2/actin disruption impairs GLUT4 trafficking elicited by insulin and hyperosmolarity. In addition to showing for the first time the important role of PIP 2-regulated cytoskeletal events in GLUT4 regulation by stimuli other than insulin, these studies reveal a novel function of PIP2/actin structure in signal transduction.

Original languageEnglish
Pages (from-to)849-856
Number of pages8
JournalJournal of Cellular Biochemistry
Volume97
Issue number4
DOIs
StatePublished - Mar 1 2006

Fingerprint

Facilitative Glucose Transport Proteins
Endothelin-1
Membranes
Insulin
Actins
Phosphatidylinositols
Phosphatidylinositol 3-Kinase
Insulin Receptor Substrate Proteins
Signal transduction
Osmotic Pressure
Cell membranes
Phosphatidylinositol 3-Kinases
Signal Transduction
Chemical activation
Cell Membrane

Keywords

  • Actin
  • Cbl
  • Insulin resistance
  • Phosphatidylinositol 4,5-bisphosphate

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

Endothelin-1 impairs glucose transporter trafficking via a membrane-based mechanism. / Strawbridge, Andrew B.; Elmendorf, Jeffrey.

In: Journal of Cellular Biochemistry, Vol. 97, No. 4, 01.03.2006, p. 849-856.

Research output: Contribution to journalArticle

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