Glucagon, from past to present: a century of intensive research and controversies.
Lancet Diabetes Endocrinol
; 11(2): 129-138, 2023 02.
Article
em En
| MEDLINE
| ID: mdl-36566754
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Diabetes Mellitus Tipo 2
/
Hipoglicemia
Limite:
Humans
Idioma:
En
Revista:
Lancet Diabetes Endocrinol
Ano de publicação:
2023
Tipo de documento:
Article