title: Insulin analogues display atypical differentiative activities in skin keratinocytes.
abstract: BACKGROUND
  We have previously shown that both insulin and IGF1 lead to increased proliferation of keratinocytes. However, whereas insulin supports keratinocytes differentiation, IGF1 inhibits this process. The aim of the present study was to examine the proliferative and differentiative effects of insulin analogues (glargine, detemir, lispro and aspart) in primary keratinocytes in comparison with insulin and IGF1.
  
  
  METHODS
  Primary keratinocytes cultures were produced from newborn BALB/c mice skin. Proliferation rates were assessed by [(3)H]-thymidine incorporation and XTT assays and differentiation was evaluated by Western blots analysis. Insulin receptor and IGF1 receptor phosphorylation was assessed by immunoprecipitation assays.
  
  
  RESULTS
  Treatment with glargine or detemir resulted in an insulin-like effect on the differentiation process whereas lispro and aspart treatment led to an IGF1-like effect. In addition, treatment of keratinocytes with aspart led to a rapid phosphorylation of the IGF1 receptor.
  
  
  CONCLUSIONS
  Our study provides evidence that insulin analogues elicit atypical actions in the skin.
authors.affiliation: Department of Pathology .
authors.forename: Ravid
authors.initials: R
authors.lastname: Solomon Zemler
authors.forename: Galina
authors.initials: G
authors.lastname: Weingarten
authors.forename: Rive
authors.initials: R
authors.lastname: Sarfstein
authors.forename: Zvi
authors.initials: Z
authors.lastname: Laron
authors.forename: Haim
authors.initials: H
authors.lastname: Werner
authors.forename: Efrat
authors.initials: E
authors.lastname: Wertheimer
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation; D049109:Cell Proliferation; D015870:Gene Expression; D061267:Insulin Aspart / Q000494:pharmacology*; D000069057:Insulin Detemir / Q000494:pharmacology*; D000069036:Insulin Glargine / Q000494:pharmacology*; D061268:Insulin Lispro / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010766:Phosphorylation / Q000187:drug effects; D061251:Primary Cell Culture; D017526:Receptor, IGF Type 1 / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D061268:Insulin Lispro; C519530:insulin-like growth factor-1, mouse; D000069036:Insulin Glargine; D000069057:Insulin Detemir; D007334:Insulin-Like Growth Factor I; D061267:Insulin Aspart; D017526:Receptor, IGF Type 1
keywords: Differentiation; insulin; insulin-like growth factor-1 (IGF1); keratinocytes; proliferation