Insulin-like growth factor-1 induces lipid production in human SEB-1 sebocytes via sterol response element-binding protein-1

J Invest Dermatol. 2006 Jun;126(6):1226-32. doi: 10.1038/sj.jid.5700278.

Abstract

An understanding of the molecular signaling involved in sebaceous gland lipid production is needed to develop therapeutic targets to improve acne. Treatment with methylisobutylxanthine, dexamethasone, and a high dose of insulin (MDI) has been shown to differentiate 3T3-L1 preadipocytes into adipocytes, a differentiation marked by an increase in lipid production. The present study has the following aims: (1) Since high doses of insulin, as found in MDI, will activate the IGF-1 receptor, we sought to determine if IGF-1 is capable of reproducing the lipogenic effect seen with MDI treatment, and (2) to determine if the sterol response element-binding protein-1 (SREBP-1) pathway mediates the increase in lipogenesis. Here we report that MDI increases lipogenesis and that this effect can be attributed wholly to the high-dose insulin in SEB-1 cells. Further, we show that a physiologically relevant dose of IGF-1 or high-dose (1 microM) insulin induces an increase in SREBP-1 mRNA, protein, and total lipid production; while 100 nM insulin induces lipogenesis yet the SREBP protein levels remain unchanged. These data indicate that activation of the IGF-1 receptor increases lipogenesis in SEB-1 cells through both SREBP-dependent and SREBP-independent pathways.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Humans
  • Insulin / pharmacology
  • Insulin-Like Growth Factor I / pharmacology*
  • Lipogenesis* / drug effects
  • Protein Isoforms / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptor, Insulin / metabolism
  • Sebaceous Glands / drug effects
  • Sebaceous Glands / metabolism*
  • Sterol Regulatory Element Binding Protein 1 / genetics
  • Sterol Regulatory Element Binding Protein 1 / metabolism*

Substances

  • Insulin
  • Protein Isoforms
  • RNA, Messenger
  • Sterol Regulatory Element Binding Protein 1
  • Insulin-Like Growth Factor I
  • Receptor, Insulin