title: Exendin-4 Promotes Beta Cell Proliferation via PI3k/Akt Signalling Pathway.
abstract: OBJECTIVE
  Prevention of diabetes requires maintenance of a functional beta-cell mass, the postnatal growth of which depends on beta cell proliferation. Past studies have shown evidence of an effect of an incretin analogue, Exendin-4, in promoting beta cell proliferation, whereas the underlying molecular mechanisms are not completely understood.
  
  
  METHODS
  Here we studied the effects of Exendin-4 on beta cell proliferation in vitro and in vivo through analysing BrdU-incorporated beta cells. We also analysed the effects of Exendin-4 on beta cell mass in vivo, and on beta cell number in vitro. Then, we applied specific inhibitors of different signalling pathways and analysed their effects on Exendin-4-induced beta cell proliferation.
  
  
  RESULTS
  Exendin-4 increased beta cell proliferation in vitro and in vivo, resulting in significant increases in beta cell mass and beta cell number, respectively. Inhibition of PI3K/Akt signalling, but not inhibition of either ERK/MAPK pathway, or JNK pathway, significantly abolished the effects of Exendin-4 in promoting beta cell proliferation.
  
  
  CONCLUSIONS
  Exendin-4 promotes beta cell proliferation via PI3k/Akt signaling pathway.
authors.affiliation: Department of Endocrinology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.
authors.forename: Chaoxun
authors.initials: C
authors.lastname: Wang
authors.forename: Xiaopan
authors.initials: X
authors.lastname: Chen
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Ding
authors.forename: Yanju
authors.initials: Y
authors.lastname: He
authors.forename: Chengying
authors.initials: C
authors.lastname: Gu
authors.forename: Ligang
authors.initials: L
authors.lastname: Zhou
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D000077270:Exenatide; D005260:Female; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014688:Venoms / Q000494:pharmacology*
chemical_list: D010455:Peptides; D014688:Venoms; D000077270:Exenatide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt