Article (Scientific journals)
Inhibiting or Antagonizing Glucagon: A Progress in Diabetes Care ?
LEFEBVRE, Pierre; Paquot, Nicolas; Scheen, André
2015In Diabetes, Obesity and Metabolism
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Abstract :
[en] Absolute or relative hyperglucagonemia has been recognized for years in all experimental or clinical forms of diabetes. It has been suggested that excess secretion of glucagon by the islet alpha-cells is a direct consequence of intra-islet insulin secretory defects. Recent studies have demonstrated that knock-out of the glucagon receptor or administration of a monoclonal specific glucagon receptor antibody make insulin deficient type 1 diabetic rodents thrive without insulin. These observations suggest that glucagon plays an essential role in the pathophysiology of diabetes and that targeting the alpha-cell and glucagon are innovative approaches in the management of diabetes. Despite active research and identification of promising compounds, no one selective glucagon antagonist is presently used in the treatment of diabetes. Interestingly, besides insulin, several drugs used today in the management of diabetes appear to exert their effects in part by inhibiting glucagon secretion (GLP-1 receptor agonists, DPP-4 inhibitors, alpha glucosidase inhibitors and, maybe, sulfonylureas) or glucagon action (metformin). The potential risks associated with total glucagon suppression include alpha-cell hyperplasia, increased mass of the pancreas, increased susceptibility to hepatosteatosis and hepatocellular injury and increased risk of hypoglycaemia and should be considered in the search and development of new compounds reducing glucagon receptor signalling. In conclusion, more than 40 years after its initial description, the hyperglucagonemia of diabetes can no longer be ignored or minimized and its correction represents an attractive way for improving diabetes management.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
LEFEBVRE, Pierre ;  Centre Hospitalier Universitaire de Liège - CHU > Diabétologie,nutrition, maladies métaboliques
Paquot, Nicolas ;  Université de Liège > Département des sciences de la santé publique > Nutrition
Scheen, André  ;  Université de Liège > Département des sciences cliniques > Diabétologie, nutrition et maladie métaboliques
Language :
English
Title :
Inhibiting or Antagonizing Glucagon: A Progress in Diabetes Care ?
Publication date :
2015
Journal title :
Diabetes, Obesity and Metabolism
ISSN :
1462-8902
eISSN :
1463-1326
Publisher :
Blackwell, Oxford, United Kingdom
Pages :
epub ahead of print
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
This article is protected by copyright. All rights reserved.
Available on ORBi :
since 03 June 2015

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