Le rôle du glucagon dans la physiopathologie du diabète

Excessive circulating glucagon levels have been reported in all forms of diabetes, clinical or experimental. The hyperglucagonemia of diabetes in man results from an excessive secretion of the hormone. It contributes to the fasting and postprandial hyperglycemia of diabetes through increased hepatic glycogenolysis and gluconeogenesis. There is strong evidence that the hyperglucagonemia of diabetes results from the deficit in insulin secretion. Recent evidence supports a major role of the paracrine relationships between the various cells within the islets of Langerhans leading Unger and Orci to consider diabetes as a “paracrinopathy”. Experimental studies strongly suggest that the hyperglucagonemia of diabetes is the consequence of the disruption of the normal insulin pulsatile secretory pattern within the islets of Langerhans. Reducing the hypersecretion of glucagon or inhibiting its effects on its target cells are currently considered as news pathways to improve metabolic control in diabetes. However, glucagon being recognized as “the first line of defence” against hypoglycemia, caution is needed regarding the potential increased risk of hypoglycaemia when the secretion of glucagon is reduced or its effects on target cells inhibited or blocked.