Insulin stimulates membrane conductance in a liver cell line: Evidence for insertion of ion channels through a phosphoinositide 3-kinase-dependent mechanism

Gordan Kilic, R. Brian Doctor, J. Gregory Fitz

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Activation of insulin receptors stimulates a rapid increase in the ion permeability of liver cells. To evaluate whether this response involves insertion of ion channels, plasma membrane turnover was measured in a model liver cell line using the fluorescent membrane marker FM1-43. Under basal conditions, the rate of constitutive membrane turnover was ∼2%min -1, and balanced exocytosis and endocytosis maintained the total cell membrane area constant. Exposure to insulin stimulated a transient increase in membrane turnover of up to 10-fold above constitutive rates. The response was concentration-dependent (0.001-10 μM). Insulin also caused a parallel increase in membrane conductance as measured by whole-cell patch clamp recording due to opening of Cl-- and K+-selective ion channels. The insulin-stimulated membrane turnover did not appear to involve the constitutive recycling compartments, suggesting that a distinct pool of vesicles may be involved. The effects of insulin on membrane turnover and membrane conductance were inhibited by blockers of phosphoinositide 3-kinase LY294002 and wortmannin or by disrupting microtubule assembly with nocodazole. Taken together, these findings indicate that insulin stimulates recruitment of new membranes through phosphoinositide 3-kinase-dependent mechanisms. Thus, regulated insertion of a separate population of ion channel-containing vesicles may represent one mechanism for mediating the changes in membrane conductance that are essential for the cellular response to insulin.

Original languageEnglish (US)
Pages (from-to)26762-26768
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number29
DOIs
StatePublished - Jul 20 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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