Gestational diabetes and the adenosine/L-arginine/nitric oxide (ALANO) pathway in human umbilical vein endothelium

Placenta. 2006 Jan;27(1):1-10. doi: 10.1016/j.placenta.2005.01.011.


Altered endothelial cell function is a key factor associated with vascular disorders and is critical in the fetal growth and development. Pregnancies affected by diseases such as gestational diabetes are associated with human umbilical vein endothelial dysfunction, a finding that has been associated with a high incidence of vascular complications during the adult life. Limited information is available addressing cellular mechanisms associated with altered human umbilical vein endothelial function in gestational diabetes. One of the key signalling pathways associated with altered vascular physiology is the synthesis of the vasodilator nitric oxide (NO) from the cationic amino acid L-arginine by the endothelium (i.e. the endothelial L-arginine/NO pathway). The activity of this signalling pathway is modulated by D-glucose, adenosine, insulin, and ATP, among other molecules, and is upregulated (transcriptional, post-transcriptional and post-translational levels) in gestational diabetes. This review focuses on the cellular and molecular mechanisms involved with elevated adenosine levels in fetal umbilical vein blood and the endothelial L-arginine/NO pathway activity in gestational diabetes. We suggest that a lower capacity of adenosine transport by the fetal endothelium in gestational diabetes leads to extracellular accumulation of this nucleoside and its higher bio-availability activates endothelial P1 type purinoceptors. A functional association between A2a purinoceptor subtype signalling and the activity of the l-arginine transport mediated by human cationic amino acid transporters and endothelial NO synthase activity (i.e. 'ALANO pathway') is proposed, revealing in part the mechanisms that account for human umbilical vein endothelial cell dysfunction programmed through the development of the fetus in gestational diabetes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosine / metabolism*
  • Animals
  • Arginine / metabolism*
  • Diabetes, Gestational / metabolism*
  • Endothelium / metabolism*
  • Female
  • Humans
  • Nitric Oxide / metabolism*
  • Pregnancy
  • Signal Transduction*
  • Umbilical Veins / metabolism*


  • Nitric Oxide
  • Arginine
  • Adenosine