title: FTY720 preserved islet β-cell mass by inhibiting apoptosis and increasing survival of β-cells in db/db mice.
abstract: BACKGROUND
  FTY720, an analogue of sphingosine-1-phosphate, has shown potential in the treatment of several autoimmune diseases, such as multiple sclerosis, type 1 diabetes and systemic lupus erythematosus. It prevents development or cure of autoimmune diabetes in animal models. Recently, we reported that FTY720 also prevents development of diabetes in db/db mice by β-cell regeneration in vivo. This study investigated the effect of FTY720 on apoptosis in β-cells in db/db mice treated with FTY720 16 weeks.
  
  
  METHODS
  Six week old female db/db mice were divided into control and FTY720 groups. FTY720 (10 mg/kg) was orally administrated daily. Body weights and fasting glucose levels were measured once a week after overnight fasting. After 16 weeks of treatment, oral glucose and insulin tolerance tests were performed, serum insulin levels and insulin contents in pancreas were determined, and then all mice were subjected to physiological and histological analyses.
  
  
  RESULTS
  FTY720-treated mice showed normal fasting glucose levels, improved glucose tolerance with normal insulin sensitivity and restored β-cell function to produce and secret insulin. Pancreas histology revealed that FTY720 prevented islet damage and preserved β-cell mass by inhibiting apoptosis and increasing β-cell survival in pancreatic islets.
  
  
  CONCLUSIONS
  We concluded that early intervention with FTY720 in db/db mice can prevent development of diabetes through preserving β-cell mass by inhibiting apoptosis and increasing survival of islet β-cells.
authors.affiliation: Anesthesiology and Pain Medicine, Catholic University of Saint Mary Hospital, Seoul, Korea.
authors.forename: Hosik
authors.initials: H
authors.lastname: Moon
authors.forename: Jinyoung
authors.initials: J
authors.lastname: Chon
authors.forename: Jindeok
authors.initials: J
authors.lastname: Joo
authors.forename: Daewoo
authors.initials: D
authors.lastname: Kim
authors.forename: Janghyeok
authors.initials: J
authors.lastname: In
authors.forename: Haejin
authors.initials: H
authors.lastname: Lee
authors.forename: Jaesik
authors.initials: J
authors.lastname: Park
authors.forename: Jinwoo
authors.initials: J
authors.lastname: Choi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology*; D005260:Female; D000068876:Fingolimod Hydrochloride; D005951:Glucose Tolerance Test; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D011409:Propylene Glycols / Q000494:pharmacology*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D007166:Immunosuppressive Agents; D007328:Insulin; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine