Insulin-like growth factor-I increases astrocyte intercellular gap junctional communication and connexin43 expression in vitro

J Neurosci Res. 2003 Oct 1;74(1):12-22. doi: 10.1002/jnr.10734.


Connexin43 (cx43) forms gap junctions in astrocytes, and these gap junctions mediate intercellular communication by providing transport of low-molecular-weight metabolites and ions. We have recently shown that systemic growth hormone increases cx43 in the brain. One possibility was that local brain insulin-like growth factor-I (IGF-I) could mediate the effect by acting directly on astrocytes. In the present study, we examined the effects of direct application of recombinant human IGF-I (rhIGF-I) on astrocytes in primary culture concerning cx43 protein expression and gap junctional communication (GJC). After 24 hr of stimulation with rhIGF-I under serum-free conditions, the GJC and cx43 protein were analyzed. Administration of 30 ng/ml rhIGF-I increased the GJC and the abundance of cx43 protein. Cell proliferation of the astrocytes was not significantly increased by rhIGF-I at this concentration. However, a higher concentration of rhIGF-I (150 ng/ml) had no effect on GJC/cx43 but increased cell proliferation. Because of the important modulatory role of IGF binding proteins (IGFBPs) on IGF-I action, we analyzed IGFBPs in conditioned media. In cultures with a low abundance of IGFBPs (especially IGFBP-2), the GJC response to 30 ng/ml rhIGF-I was 81%, compared with the average of 25%. Finally, as a control, insulin was given in equimolar concentrations. However, GJC was not affected, which suggests that rhIGF-I acted via IGF-I receptors. In summary, the data show that rhIGF-I may increase GJC/cx43, whereas a higher concentration of rhIGF-I--at which stimulation of proliferation occurred--did not affect GJC/cx43. Furthermore, IGFBP-2 appeared to modulate the action of rhIGF-I on GJC in astrocytes by a paracrine mechanism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / drug effects*
  • Astrocytes / metabolism
  • Cell Communication / drug effects*
  • Cell Communication / physiology
  • Cells, Cultured
  • Connexin 43 / biosynthesis*
  • Connexin 43 / genetics
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Humans
  • Insulin-Like Growth Factor I / pharmacology*
  • Insulin-Like Growth Factor I / physiology
  • Intercellular Junctions / drug effects*
  • Intercellular Junctions / metabolism
  • Intercellular Signaling Peptides and Proteins / pharmacology
  • Intercellular Signaling Peptides and Proteins / physiology
  • Rats
  • Rats, Sprague-Dawley


  • Connexin 43
  • Intercellular Signaling Peptides and Proteins
  • myotrophin
  • Insulin-Like Growth Factor I