title: Osthole activates glucose uptake but blocks full activation in L929 fibroblast cells, and inhibits uptake in HCLE cells.
abstract: OBJECTIVE
  Osthole, a coumarin derivative, has been used in Chinese medicine and studies have suggested a potential use in treatment of diabetes and cancers. Therefore, we investigated the effects of osthole and other coumarins on GLUT1 activity in two cell lines that exclusively express GLUT1.
  
  
  METHODS
  We measured the magnitude and time frame of the effects of osthole and related coumarins on glucose uptake in two cells lines; L929 fibroblast cells which have low GLUT1 expression levels and low basal glucose uptake and HCLE cells which have high GLUT1 concentrations and high basal uptake. We also explored the effects of these coumarins in combination with other GLUT1 activators.
  
  
  RESULTS
  Osthole activates glucose uptake in L929 cells with a modest maximum 1.7-fold activation achieved by 50 μM with both activation and recovery occurring within minutes. However, osthole blocks full acute activation of glucose uptake by other, more robust activators. This behavior mimics the effects of other thiol reactive compounds and suggests that osthole is interacting with cysteine residues, possibly within GLUT1 itself. Coumarin, 7-hydroxycoumarin, and 7-methoxycoumarin, do not affect glucose uptake, which is consistent with the notion that the isoprenoid structure in osthole may be important to gain membrane access to GLUT1. In contrast to its effects in L929 cells, osthole inhibits basal glucose uptake in the more active HCLE cells.
  
  
  CONCLUSIONS
  The differential effects of osthole in L929 and HCLE cells indicated that regulation of GLUT1 varies, likely depending on its membrane concentration.
authors.affiliation: Department of Chemistry and Biochemistry, Calvin College, Grand Rapids, MI 49546, USA.
authors.forename: Ola D
authors.initials: OD
authors.lastname: Alabi
authors.affiliation: Department of Chemistry and Biochemistry, Calvin College, Grand Rapids, MI 49546, USA.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Gunnink
authors.affiliation: Department of Chemistry and Biochemistry, Calvin College, Grand Rapids, MI 49546, USA.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Kuiper
authors.affiliation: Department of Chemistry and Biochemistry, Calvin College, Grand Rapids, MI 49546, USA.
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Kerk
authors.affiliation: Department of Chemistry and Biochemistry, Calvin College, Grand Rapids, MI 49546, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Braun
authors.affiliation: Department of Chemistry and Biochemistry, Calvin College, Grand Rapids, MI 49546, USA. Electronic address: lout@calvin.edu.
authors.forename: Larry L
authors.initials: LL
authors.lastname: Louters
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002461:Cell Line, Transformed; D003374:Coumarins / Q000737:chemistry* / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism*; D005947:Glucose / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D006801:Humans; D051379:Mice
chemical_list: D003374:Coumarins; D005947:Glucose; C046627:osthol
keywords: Acute activation; GLUT1; Glucose uptake; Membrane transport; Osthole and coumarins