All-trans retinoic acid ameliorates glycemic control in diabetic mice via modulating pancreatic islet production of vascular endothelial growth factor-A

• Published in: Biochemical and biophysical research communications 2016-09, Vol.477 (4), p.874-880
• Main Authors: Chien, Chiao-Yun, Yuan, Tze-An, Cho, Candy Hsin-Hua, Chang, Fang-Pei, Mao, Wan-Yu, Wu, Ruei-Ren, Lee, Hsuan-Shu, Shen, Chia-Ning
• Format: Article
• Language: English
• Subjects: All-trans retinoic acid; animal disease models; Animals; AtRA; blood glucose; Blood Glucose - metabolism; Diabetes Mellitus, Type 1 - diagnosis; Diabetes Mellitus, Type 1 - drug therapy; Diabetes Mellitus, Type 1 - metabolism; disease control; Dose-Response Relationship, Drug; glycemic control; hyperglycemia; Hypoglycemic Agents - administration & dosage; insulin; Insulin - blood; insulin-dependent diabetes mellitus; Islet vascularization; islets of Langerhans; Islets of Langerhans - drug effects; Islets of Langerhans - metabolism; laminin; Male; metabolites; Mice; patients; RAR; retinoic acid; Streptozocin; streptozotocin; STZ; T1DM; Treatment Outcome; Tretinoin - administration & dosage; Type 1 diabetes mellitus; Vascular endothelial growth factor; vascular endothelial growth factor A; Vascular Endothelial Growth Factor A - metabolism; VEGF-A; vitamin A; vitamin metabolism
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2016.06.151

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. •AtRA administration ameliorates the blood glucose level of diabetic mice.•AtRA enhances islet vascularization in diabetic mice.•AtRA elevates vascular endothelial growth factor production in islets.•AtRA improves islet graft vascularization and ameliorates hyperglycemia in diabetic mice.