Imperial College London

Professor Sir Steve Bloom FMedSci, FRS

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Departmental Academic REF2014 Lead
 
 
 
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Contact

 

+44 (0)20 7594 9048s.bloom Website

 
 
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Assistant

 

Ms Keda Price-Cousins +44 (0)20 7594 9048

 
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Location

 

6N3Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Wewer:2023:10.1007/s00125-023-05947-y,
author = {Wewer, Albrechtsen NJ and Holst, JJ and Cherrington, AD and Finan, B and Gluud, LL and Dean, ED and Campbell, JE and Bloom, SR and Tan, TM-M and Knop, FK and Müller, TD},
doi = {10.1007/s00125-023-05947-y},
journal = {Diabetologia},
pages = {1378--1394},
title = {100 years of glucagon and 100 more.},
url = {http://dx.doi.org/10.1007/s00125-023-05947-y},
volume = {66},
year = {2023}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - The peptide hormone glucagon, discovered in late 1922, is secreted from pancreatic alpha cells and is an essential regulator of metabolic homeostasis. This review summarises experiences since the discovery of glucagon regarding basic and clinical aspects of this hormone and speculations on the future directions for glucagon biology and glucagon-based therapies. The review was based on the international glucagon conference, entitled 'A hundred years with glucagon and a hundred more', held in Copenhagen, Denmark, in November 2022. The scientific and therapeutic focus of glucagon biology has mainly been related to its role in diabetes. In type 1 diabetes, the glucose-raising properties of glucagon have been leveraged to therapeutically restore hypoglycaemia. The hyperglucagonaemia evident in type 2 diabetes has been proposed to contribute to hyperglycaemia, raising questions regarding underlying mechanism and the importance of this in the pathogenesis of diabetes. Mimicry experiments of glucagon signalling have fuelled the development of several pharmacological compounds including glucagon receptor (GCGR) antagonists, GCGR agonists and, more recently, dual and triple receptor agonists combining glucagon and incretin hormone receptor agonism. From these studies and from earlier observations in extreme cases of either glucagon deficiency or excess secretion, the physiological role of glucagon has expanded to also involve hepatic protein and lipid metabolism. The interplay between the pancreas and the liver, known as the liver-alpha cell axis, reflects the importance of glucagon for glucose, amino acid and lipid metabolism. In individuals with diabetes and fatty liver diseases, glucagon's hepatic actions may be partly impaired resulting in elevated levels of glucagonotropic amino acids, dyslipidaemia and hyperglucagonaemia, reflecting a new, so far largely unexplored pathophysiological phenomenon termed 'glucagon resistance'. Importantly, the hyperglucagonaemia as part of
AU - Wewer,Albrechtsen NJ
AU - Holst,JJ
AU - Cherrington,AD
AU - Finan,B
AU - Gluud,LL
AU - Dean,ED
AU - Campbell,JE
AU - Bloom,SR
AU - Tan,TM-M
AU - Knop,FK
AU - Müller,TD
DO - 10.1007/s00125-023-05947-y
EP - 1394
PY - 2023///
SP - 1378
TI - 100 years of glucagon and 100 more.
T2 - Diabetologia
UR - http://dx.doi.org/10.1007/s00125-023-05947-y
UR - https://www.ncbi.nlm.nih.gov/pubmed/37367959
VL - 66
ER -