Physiology of the Incretin Hormones, GIP and GLP-1-Regulation of Release and Posttranslational Modifications
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Physiology of the Incretin Hormones, GIP and GLP-1-Regulation of Release and Posttranslational Modifications. / Holst, Jens J.; Albrechtsen, Nicolai J. Wewer; Rosenkilde, Mette M.; Deacon, Carolyn F.
In: Comprehensive Physiology, Vol. 9, No. 4, 2019, p. 1339-1381.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Physiology of the Incretin Hormones, GIP and GLP-1-Regulation of Release and Posttranslational Modifications
AU - Holst, Jens J.
AU - Albrechtsen, Nicolai J. Wewer
AU - Rosenkilde, Mette M.
AU - Deacon, Carolyn F.
PY - 2019
Y1 - 2019
N2 - The focus of this article is on the analysis of the release and postrelease fate of the incretin hormones, glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide. Their actions are dealt with to the extent that they are linked to their secretion. For both hormones, their post-translational processing is analyzed in detail, because of its importance for the understanding of the molecular heterogeneity of the hormones. Methods of analysis, in particular regarding measurements in plasma from in vivo experiments, are discussed in detail in relation to the molecular heterogeneity of the hormones, and the importance of the designations "total" versus "intact hormones" is explained. Both hormones are substrates for the ubiquitous enzyme, dipeptidyl peptidase-4, which inactivates the peptides with dramatic consequences for their physiological spectrum of activities. The role of endogenous and exogenous antagonists of the receptors is discussed in detail because of their importance for the elucidation of the physiology and pathophysiology of the hormones. Regarding the actual secretion, the most important factors are discussed, including gastric emptying rate and the influence of the different macronutrients. Additional factors discussed are the role of bile, paracrine regulation, the role of the microbiota, pharmaceuticals, and exercise. Finally, the secretion during pathological conditions is discussed. (c) 2019 American Physiological Society.
AB - The focus of this article is on the analysis of the release and postrelease fate of the incretin hormones, glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide. Their actions are dealt with to the extent that they are linked to their secretion. For both hormones, their post-translational processing is analyzed in detail, because of its importance for the understanding of the molecular heterogeneity of the hormones. Methods of analysis, in particular regarding measurements in plasma from in vivo experiments, are discussed in detail in relation to the molecular heterogeneity of the hormones, and the importance of the designations "total" versus "intact hormones" is explained. Both hormones are substrates for the ubiquitous enzyme, dipeptidyl peptidase-4, which inactivates the peptides with dramatic consequences for their physiological spectrum of activities. The role of endogenous and exogenous antagonists of the receptors is discussed in detail because of their importance for the elucidation of the physiology and pathophysiology of the hormones. Regarding the actual secretion, the most important factors are discussed, including gastric emptying rate and the influence of the different macronutrients. Additional factors discussed are the role of bile, paracrine regulation, the role of the microbiota, pharmaceuticals, and exercise. Finally, the secretion during pathological conditions is discussed. (c) 2019 American Physiological Society.
U2 - 10.1002/cphy.c180013
DO - 10.1002/cphy.c180013
M3 - Journal article
C2 - 31688969
VL - 9
SP - 1339
EP - 1381
JO - Comprehensive Physiology
JF - Comprehensive Physiology
SN - 2040-4603
IS - 4
ER -
ID: 236610019