Protective effect of phosphatidylinositol 4,5-bisphosphate against cortical filamentous actin loss and insulin resistance induced by sustained exposure of 3T3-L1 adipocytes to insulin

Guoli Chen, Priya Raman, Padma Bhonagiri, Andrew B. Strawbridge, Guruprasad R. Pattar, Jeffrey S. Elmendorf

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

Muscle and fat cells develop insulin resistance when cultured under hyperinsulinemic conditions for sustained periods. Recent data indicate that early insulin signaling defects do not fully account for the loss of insulin action. Given that cortical filamentous actin (F-actin) represents an essential aspect of insulin regulated glucose transport, we tested to see whether cortical F-actin structure was compromised during chronic insulin treatment. The acute effect of insulin on GLUT4 translocation and glucose uptake was diminished in 3T3-L1 adipocytes exposed to a physiological level of insulin (5 nM) for 12 h. This insulin-induced loss of insulin responsiveness was apparent under both low (5.5 mM) and high (25 mM) glucose concentrations. Microscopic and biochemical analyses revealed that the hyperinsulinemic state caused a marked loss of cortical F-actin. Since recent data link phosphatidylinositol 4,5-bisphosphate (PIP2) to actin cytoskeletal mechanics, we tested to see whether the insulin-resistant condition affected PIP2 and found a noticeable loss of this lipid from the plasma membrane. Using a PIP2 delivery system, we replenished plasma membrane PIP2 in cells following the sustained insulin treatment and observed a restoration in cortical F-actin and insulin responsiveness. These data reveal a novel molecular aspect of insulin-induced insulin resistance involving defects in PIP2/actin regulation.

Original languageEnglish (US)
Pages (from-to)39705-39709
Number of pages5
JournalJournal of Biological Chemistry
Volume279
Issue number38
DOIs
StatePublished - Sep 17 2004

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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