title: All-trans retinoic acid ameliorates glycemic control in diabetic mice via modulating pancreatic islet production of vascular endothelial growth factor-A.
abstract: Patients with type 1 diabetes mellitus are associated with impairment in vitamin A metabolism. This study evaluated whether treatment with retinoic acid, the biologically active metabolite of vitamin A, can ameliorate diabetes. All-trans retinoic acid (atRA) was used to treat streptozotocin (STZ)-induced diabetic mice which revealed atRA administration ameliorated blood glucose levels of diabetic mice. This hyperglycemic amelioration was accompanied by an increase in the amount of β cells co-expressed Pdx1 and insulin and by restoration of the vascular laminin expression. The atRA-induced production of vascular endothelial growth factor-A from the pancreatic islets was possibly the key factor that mediated the restoration of islet vascularity and recovery of β-cell mass. Furthermore, the combination of islet transplantation and atRA administration significantly rescued hyperglycemia in diabetic mice. These findings suggest that vitamin A derivatives can potentially be used as a supplementary treatment to improve diabetes management and glycemic control.
authors.affiliation: Genomics Research Center, Academia Sinica, Nankang, Taipei, 115, Taiwan; Institute of Biotechnology, National Taiwan University, Taipei, 106, Taiwan.
authors.forename: Chiao-Yun
authors.initials: CY
authors.lastname: Chien
authors.affiliation: Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, 112, Taiwan.
authors.forename: Tze-An
authors.initials: TA
authors.lastname: Yuan
authors.affiliation: Genomics Research Center, Academia Sinica, Nankang, Taipei, 115, Taiwan.
authors.forename: Candy Hsin-Hua
authors.initials: CH
authors.lastname: Cho
authors.affiliation: Genomics Research Center, Academia Sinica, Nankang, Taipei, 115, Taiwan.
authors.forename: Fang-Pei
authors.initials: FP
authors.lastname: Chang
authors.affiliation: Genomics Research Center, Academia Sinica, Nankang, Taipei, 115, Taiwan.
authors.forename: Wan-Yu
authors.initials: WY
authors.lastname: Mao
authors.affiliation: Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, 112, Taiwan.
authors.forename: Ruei-Ren
authors.initials: RR
authors.lastname: Wu
authors.affiliation: Institute of Biotechnology, National Taiwan University, Taipei, 106, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, 100, Taiwan. Electronic address: benlee@ntu.edu.tw.
authors.forename: Hsuan-Shu
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Genomics Research Center, Academia Sinica, Nankang, Taipei, 115, Taiwan; Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, 112, Taiwan. Electronic address: cnshen@gate.sinica.edu.tw.
authors.forename: Chia-Ning
authors.initials: CN
authors.lastname: Shen
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D013311:Streptozocin; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D014212:Tretinoin; D013311:Streptozocin
keywords: All-trans retinoic acid; Islet vascularization; Type 1 diabetes mellitus; Vascular endothelial growth factor