Insulin-like growth factor-1 induces lipid production in human SEB-1 sebocytes via sterol response element-binding protein-1.
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.
The Jake Gittlen Cancer Research Foundation, Hershey, Pennsylvania, USA.
Terry M
TM
Smith
Zhaoyuan
Z
Cong
Kathryn L
KL
Gilliland
Gary A
GA
Clawson
Diane M
DM
Thiboutot
D002478:Cells, Cultured; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D050155:Lipogenesis / Q000187:drug effects; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism; D012627:Sebaceous Glands / Q000187:drug effects / Q000378:metabolism*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism*
D007328:Insulin; D020033:Protein Isoforms; D012333:RNA, Messenger; D051780:Sterol Regulatory Element Binding Protein 1; D007334:Insulin-Like Growth Factor I; D011972:Receptor, Insulin