Article ; Online: Glucagon, from past to present: a century of intensive research and controversies.
The lancet. Diabetes & endocrinology
2022 Volume 11, Issue 2, Page(s) 129–138
Abstract: 2022 corresponds to the 100th anniversary of the discovery of glucagon. This TimeCapsule aims to recall the main steps leading to the discovery, characterisation, and clinical importance of the so-called second pancreatic hormone. We describe the early ... ...
| Abstract | 2022 corresponds to the 100th anniversary of the discovery of glucagon. This TimeCapsule aims to recall the main steps leading to the discovery, characterisation, and clinical importance of the so-called second pancreatic hormone. We describe the early historical findings in basic research (ie, discovery, purification, structure, α-cell origin, radioimmunoassay, glucagon gene [GCG], and glucagon receptor [GLR]), in which three future Nobel Prize laureates were actively involved. Considered as an anti-insulin hormone, glucagon was rapidly used to treat insulin-induced hypoglycaemic coma episodes in people with type 1 diabetes. A key step in the story of glucagon was the discovery of its role and the role of α cells in the physiology and pathophysiology (ie, paracrinopathy) of type 2 diabetes. This concept led to the design of different strategies targeting glucagon, among which GLP-1 receptor (GLP1R) agonists were a major breakthrough, and combination of inhibition of glucagon secretion with stimulation of insulin secretion (both in a glucose-dependent manner). Taking advantage of the glucagon-induced increase in energy metabolism, biased coagonists were developed. Besides the GLP-1 receptor, these coagonists also target the glucagon receptor to further promote weight loss. Thus, the 100-year story of glucagon has most probably not come to an end. |
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| MeSH term(s) | Humans ; Glucagon/physiology ; Receptors, Glucagon/agonists ; Receptors, Glucagon/genetics ; Diabetes Mellitus, Type 2/metabolism ; Glucagon-Like Peptide-1 Receptor ; Glucagon-Like Peptide 1/metabolism ; Hypoglycemia |
| Chemical Substances | Glucagon (9007-92-5) ; Receptors, Glucagon ; Glucagon-Like Peptide-1 Receptor ; Glucagon-Like Peptide 1 (89750-14-1) |
| Language | English |
| Publishing date | 2022-12-22 |
| Publishing country | England |
| Document type | Journal Article ; Review |
| ISSN | 2213-8595 |
| ISSN (online) | 2213-8595 |
| DOI | 10.1016/S2213-8587(22)00349-7 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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