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

Biochem Biophys Res Commun. 2016 Sep 2;477(4):874-880. doi: 10.1016/j.bbrc.2016.06.151. Epub 2016 Jul 2.

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.

Keywords: All-trans retinoic acid; Islet vascularization; Type 1 diabetes mellitus; Vascular endothelial growth factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 1 / diagnosis*
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / metabolism*
  • Dose-Response Relationship, Drug
  • Hypoglycemic Agents / administration & dosage
  • Insulin / blood
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Male
  • Mice
  • Streptozocin
  • Treatment Outcome
  • Tretinoin / administration & dosage*
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, mouse
  • Tretinoin
  • Streptozocin