Insulin/adenosine axis linked signalling

Mol Aspects Med. 2017 Jun:55:45-61. doi: 10.1016/j.mam.2016.11.002. Epub 2016 Nov 19.

Abstract

Regulation of blood flow depends on systemic and local release of vasoactive molecules such as insulin and adenosine. These molecules cause vasodilation by activation of plasma membrane receptors at the vascular endothelium. Adenosine activates at least four subtypes of adenosine receptors (A1AR, A2AAR, A2BAR, A3AR), of which A2AAR and A2BAR activation leads to increased cAMP level, generation of nitric oxide, and relaxation of the underlying smooth muscle cell layer. Vasodilation caused by adenosine also depends on plasma membrane hyperpolarization due to either activation of intermediate-conductance Ca2+-activated K+ channels in vascular smooth muscle or activation of ATP-activated K+ channels in the endothelium. Adenosine also causes vasoconstriction via a mechanism involving A1AR activation resulting in lower cAMP level and increased thromboxane release. Insulin has also a dual effect causing NO-dependent vasodilation, but also sympathetic activity- and increased endothelin 1 release-dependent vasoconstriction. Interestingly, insulin effects require or are increased by activation or inactivation of adenosine receptors. This is phenomenon described for d-glucose and l-arginine transport where A2AAR and A2BAR play a major role. Other studies show that A1AR activation could reduce insulin release from pancreatic β-cells. Whether adenosine modulation of insulin biological effect is a phenomenon that depends on co-localization of adenosine receptors and insulin receptors, and adenosine plasma membrane transporters is something still unclear. This review summarizes findings addressing potential involvement of adenosine receptors to modulate insulin effect via insulin receptors with emphasis in the human vasculature.

Keywords: Adenosine; Endothelium; Insulin; Smooth muscle; Vascular.

Publication types

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

MeSH terms

  • Adenosine / genetics
  • Adenosine / metabolism*
  • Endothelium, Vascular / metabolism*
  • Endothelium, Vascular / pathology
  • Glucose / metabolism
  • Humans
  • Insulin / genetics
  • Insulin / metabolism*
  • Muscle, Smooth, Vascular / metabolism
  • Nitric Oxide / metabolism
  • Receptor, Adenosine A2A / genetics
  • Receptor, Adenosine A2A / metabolism
  • Receptor, Adenosine A2B / genetics
  • Receptor, Adenosine A2B / metabolism
  • Receptor, Adenosine A3 / genetics
  • Receptor, Adenosine A3 / metabolism
  • Signal Transduction
  • Vasoconstriction / genetics

Substances

  • Insulin
  • Receptor, Adenosine A2A
  • Receptor, Adenosine A2B
  • Receptor, Adenosine A3
  • Nitric Oxide
  • Glucose
  • Adenosine