title: Pax4 Expression does not Transduce Pancreatic Alpha Cells to Beta Cells.
abstract: OBJECTIVE
  The lack of available beta cells greatly limits the use of beta cell transplantation as a therapy for diabetes. Thus, generation of beta cells from other sources is substantially required. Pax4 has been shown to induce reprograming of alpha cells into beta cells during embryogenesis. Nevertheless, whether expression of Pax4 in adult alpha cells could trigger this alpha-to-beta cell reprogramming is unknown.
  
  
  METHODS
  Here we generated an adeno-associated virus carrying Pax4 and GFP under a CMV promoter (AAV-Pax4). We used AAV-Pax4 to transduce a mouse alpha cell line in vitro, and to transduce primary alpha cells in diabetic mice. Reprogramming was examined by double immunostaining and by changes in beta cell number. The effects on blood glucose were evaluated by fasting blood glucose and glucose response.
  
  
  RESULTS
  In vitro, Pax4 overexpression neither induced insulin expression, nor suppressed glucagon expression in alpha cells. In vivo, Pax4 overexpression failed to increase beta cell number, and did not alter hyperglycemia and glucose response in diabetic mice.
  
  
  CONCLUSIONS
  Pax4 expression is not sufficient to transduce pancreatic alpha cells into beta cells. Overexpression of Pax4 in alpha cells may not increase functional beta cell number in diabetic patients.
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yaping
authors.initials: Y
authors.lastname: Chu
authors.forename: Bing
authors.initials: B
authors.lastname: Song
authors.forename: Wang
authors.initials: W
authors.lastname: Cai
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D000229:Dependovirus / Q000235:genetics; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000502:physiology*; D010179:Pancreas / Q000166:cytology* / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D018398:Homeodomain Proteins; D051761:Paired Box Transcription Factors; C110218:Pax4 protein, mouse; D049452:Green Fluorescent Proteins