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Am J Physiol Endocrinol Metab (December 30, 2008). doi:10.1152/ajpendo.90887.2008
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Submitted on February 22, 2008
Revised on December 24, 2008
Accepted on December 24, 2008

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

Safina Ali1 and Daniel J. Drucker2*

1 SLRI
2 Mt. Sinai Hospital

* To whom correspondence should be addressed. E-mail: d.drucker{at}utoronto.ca.

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 (Gcgr) activity represents a potential target for the treatment of T2DM. Herein we review current concepts of glucagon action in hepatic and extra-hepatic tissues and evaluate the therapeutic potential, mechanisms of action, and safety of reducing Gcgr signaling for the treatment of type 2 diabetes






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