Ketosis-Prone Atypical Diabetes: Glucagon Is There, Too

Glucagon’s Golden Jubilee at the University of Liège

“…Disruption of this mechanism would be a key factor in the pathophysiology of diabetes. This concept is supported by the microanatomy of islets in rodents 19 and in man 20 where, as we have recently discussed 2, 21 the α-cell appear to be under the control of neighbouring β-cells. Further support to this theory has been brought by our observation, with the group of Peter Butler, that a 60% reduction of the β-cell mass in minipigs results in a decrease in the amplitude of the insulin pulses in the portal blood associated with a significant increase of the intraportal glucagon pulses.…”

“…22 In this model, mathematical analysis has suggested that, in normal animals, intra-islet pulsatile insulin directly suppresses glucagon secretion, but that this association is lost after selective partial reduction in β-cell mass thus supporting the concept that diabetes should indeed be considered as a paracrinopathy of the islets of Langerhans. 2,18,21 …”

“…At the time Cliff Bailey invited me to write a “personal reflection” on any aspect of diabetes I realized that my interest for glucagon spans now over fifty years with a first paper in 1960 1 and the most recent, hopefully not the last…, in 2012. 2 During that 52 year period, our Laboratory produced 69 original articles and 79 invited chapters and reviews in the title of which the word “glucagon” appeared…The present invited contribution will by no means be another review on glucagon, several are available in the current literature 3 but rather a totally biased narration of our personal journey in the field. When we did our first study in 1959-1960, Sutherland and De Duve had established that the α-cells of the pancreas were the main source of glucagon, Foà and his co-workers had conducted elegant cross-circulation experiments in anesthetized dogs and suggested that hypoglycaemia was triggering the release of glucagon by the pancreas while Bromer and his co-workers, at the Eli Lilly Laboratories in Indianapolis, had isolated, purified, crystallized and determined the primary structure of glucagon but it was not yet recognized as a bona fide hormone……”

Inhibiting or antagonizing glucagon: making progress in diabetes care

“…Numerous studies have shown that failure of glucagon suppression contributes to postprandial hyperglycaemia in type 1 and type 2 diabetes . Impaired glucagon suppression concurs with impaired insulin release to the excessive blood glucose levels in early type 1 diabetes , in impaired glucose tolerance and in ketosis‐prone atypical diabetes . Morphological studies have now firmly established that the main abnormality in the islet cell population of human diabetes is a decrease in the β‐cell mass with a relative expansion of the α‐cell mass .…”