The New Biology and Pharmacology of Glucagon
Publikation: Bidrag til tidsskrift › Review › Forskning › fagfællebedømt
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The New Biology and Pharmacology of Glucagon. / Müller, T D; Finan, B; Clemmensen, C; DiMarchi, R D; Tschöp, M H.
I: Physiological Reviews, Bind 97, Nr. 2, 04.2017, s. 721-766.Publikation: Bidrag til tidsskrift › Review › Forskning › fagfællebedømt
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TY - JOUR
T1 - The New Biology and Pharmacology of Glucagon
AU - Müller, T D
AU - Finan, B
AU - Clemmensen, C
AU - DiMarchi, R D
AU - Tschöp, M H
N1 - Copyright © 2017 the American Physiological Society.
PY - 2017/4
Y1 - 2017/4
N2 - In the last two decades we have witnessed sizable progress in defining the role of gastrointestinal signals in the control of glucose and energy homeostasis. Specifically, the molecular basis of the huge metabolic benefits in bariatric surgery is emerging while novel incretin-based medicines based on endogenous hormones such as glucagon-like peptide 1 and pancreas-derived amylin are improving diabetes management. These and related developments have fostered the discovery of novel insights into endocrine control of systemic metabolism, and in particular a deeper understanding of the importance of communication across vital organs, and specifically the gut-brain-pancreas-liver network. Paradoxically, the pancreatic peptide glucagon has reemerged in this period among a plethora of newly identified metabolic macromolecules, and new data complement and challenge its historical position as a gut hormone involved in metabolic control. The synthesis of glucagon analogs that are biophysically stable and soluble in aqueous solutions has promoted biological study that has enriched our understanding of glucagon biology and ironically recruited glucagon agonism as a central element to lower body weight in the treatment of metabolic disease. This review summarizes the extensive historical record and the more recent provocative direction that integrates the prominent role of glucagon in glucose elevation with its under-acknowledged effects on lipids, body weight, and vascular health that have implications for the pathophysiology of metabolic diseases, and the emergence of precision medicines to treat metabolic diseases.
AB - In the last two decades we have witnessed sizable progress in defining the role of gastrointestinal signals in the control of glucose and energy homeostasis. Specifically, the molecular basis of the huge metabolic benefits in bariatric surgery is emerging while novel incretin-based medicines based on endogenous hormones such as glucagon-like peptide 1 and pancreas-derived amylin are improving diabetes management. These and related developments have fostered the discovery of novel insights into endocrine control of systemic metabolism, and in particular a deeper understanding of the importance of communication across vital organs, and specifically the gut-brain-pancreas-liver network. Paradoxically, the pancreatic peptide glucagon has reemerged in this period among a plethora of newly identified metabolic macromolecules, and new data complement and challenge its historical position as a gut hormone involved in metabolic control. The synthesis of glucagon analogs that are biophysically stable and soluble in aqueous solutions has promoted biological study that has enriched our understanding of glucagon biology and ironically recruited glucagon agonism as a central element to lower body weight in the treatment of metabolic disease. This review summarizes the extensive historical record and the more recent provocative direction that integrates the prominent role of glucagon in glucose elevation with its under-acknowledged effects on lipids, body weight, and vascular health that have implications for the pathophysiology of metabolic diseases, and the emergence of precision medicines to treat metabolic diseases.
KW - Animals
KW - Brain
KW - Gastrointestinal Tract
KW - Glucagon
KW - Homeostasis
KW - Humans
KW - Liver
KW - Metabolic Diseases
KW - Pancreas
KW - Journal Article
KW - Review
U2 - 10.1152/physrev.00025.2016
DO - 10.1152/physrev.00025.2016
M3 - Review
C2 - 28275047
VL - 97
SP - 721
EP - 766
JO - Physiological Reviews
JF - Physiological Reviews
SN - 0031-9333
IS - 2
ER -
ID: 186639694