P2X receptor-ion channels in the inflammatory response in adipose tissue and pancreas-potential triggers in onset of type 2 diabetes?

Curr Opin Immunol. 2018 Jun:52:1-7. doi: 10.1016/j.coi.2018.02.002. Epub 2018 Mar 6.

Abstract

Type 2 diabetes is reaching an alarming prevalence worldwide. Its complex pathogenesis certainly includes a pivotal role of low-grade inflammation, which could be triggered by excessive purinergic signaling. In this complex scenario, extracellular ATP impairs the function of two key players: β-cell and adipose tissue. In the former, P2Y and possibly some P2X receptors-ion channels regulate insulin secretion, but it is still debated whether excessive ATP can via P2X receptors impair β-cell function directly or whether cell damage is due to an excessive systemic release of cytokines. In human adipocytes, the P2X7 receptor promotes the release of inflammatory cytokines, at least in part via inflammasome activation, likely contributing to systemic insulin resistance. This receptor-inflammasome system is also strongly activated in macrophages infiltrating both pancreas and adipose tissue, mediating a deleterious cross-talk that perpetuates the damage.

Publication types

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

MeSH terms

  • Adipocytes / metabolism
  • Adipose Tissue / metabolism*
  • Adipose Tissue / pathology
  • Animals
  • Diabetes Mellitus, Type 2 / etiology*
  • Diabetes Mellitus, Type 2 / metabolism*
  • Humans
  • Inflammation / metabolism*
  • Insulin-Secreting Cells / metabolism
  • Macrophages / immunology
  • Macrophages / metabolism
  • Pancreas / metabolism*
  • Pancreas / pathology
  • Receptors, Purinergic P2X / metabolism*

Substances

  • Receptors, Purinergic P2X