Benefits and limitations of reducing glucagon action for the treatment of type 2 diabetes.
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.
Ali
Safina
S
Mt. Sinai Hospital, Toronto, ON, Canada M5T 3L9.
Drucker
Daniel J
DJ
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000628:therapy*; D005934:Glucagon / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism / Q000628:therapy; D018027:Receptors, Glucagon / Q000235:genetics / Q000378:metabolism*
D018027:Receptors, Glucagon; D005934:Glucagon