Benefits and limitations of reducing glucagon action for the treatment of type 2 diabetes

Am J Physiol Endocrinol Metab. 2009 Mar;296(3):E415-21. doi: 10.1152/ajpendo.90887.2008. Epub 2008 Dec 30.


Glucagon is secreted from the alpha-cells of the pancreatic islets and regulates glucose homeostasis through modulation of hepatic glucose production. As elevated glucagon levels contribute to the pathophysiology of hyperglycemia in subjects with type 2 diabetes, reduction of glucagon receptor gene (Gcgr) activity represents a potential target for the treatment of T2DM. Herein, we review current concepts of glucagon action in hepatic and extrahepatic tissues and evaluate the therapeutic potential, mechanisms of action, and safety of reducing Gcgr signaling for the treatment of T2DM.

Publication types

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

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / therapy*
  • Glucagon / metabolism*
  • Humans
  • Hyperglycemia / metabolism
  • Hyperglycemia / therapy
  • Receptors, Glucagon / genetics
  • Receptors, Glucagon / metabolism*


  • Receptors, Glucagon
  • Glucagon