Metabolism of GIP and the contribution of GIP to the glucose-lowering properties of DPP-4 inhibitors.


Journal

Peptides
ISSN: 1873-5169
Titre abrégé: Peptides
Pays: United States
ID NLM: 8008690

Informations de publication

Date de publication:
03 2020
Historique:
received: 27 08 2019
revised: 05 11 2019
accepted: 06 11 2019
pubmed: 11 11 2019
medline: 9 2 2021
entrez: 11 11 2019
Statut: ppublish

Résumé

Glucose-dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone with insulinotropic and glucagonotropic actions, and is believed to be the more physiologically important incretin hormone in healthy humans. Together with the other incretin hormone, glucagon-like peptide-1 (GLP-1), it plays an important role in regulating glucose homeostasis. Both GLP-1 and GIP are substrates of the enzyme dipeptidyl peptidase-4 (DPP-4), and DPP-4 inhibitors, which potentiate their effects on glycaemic control, are now used to treat type 2 diabetes (T2D). This review describes how post-translational processing of the GIP precursor molecule and post-release degradation of the secretory products give rise to multiple isoforms of GIP, some, but not all of which are biologically active, and discusses how this impacts upon their measurement by immunological- and bioassay-based methods. DPP-4 inhibitors reduce degradation of GIP, and although the insulinotropic effects of GIP are impaired in patients with T2D, they can be at least partially restored if glycaemic control is improved. Therefore, given that studies with incretin receptor antagonists indicate that not all of the glucose-lowering effects of DPP-4 inhibition can be accounted for by GLP-1 alone, evidence supports the notion that GIP may play a role in mediating the anti-hyperglycaemic effects of DPP-4 inhibition, while its glucagonotropic actions at lower glucose levels may contribute to the low risk of hypoglycaemia associated with DPP-4 inhibitors.

Identifiants

pubmed: 31706956
pii: S0196-9781(19)30174-3
doi: 10.1016/j.peptides.2019.170196
pii:
doi:

Substances chimiques

Blood Glucose 0
Dipeptidyl-Peptidase IV Inhibitors 0
Gastrointestinal Agents 0
Gastric Inhibitory Polypeptide 59392-49-3
Dipeptidyl Peptidase 4 EC 3.4.14.5

Types de publication

Journal Article Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

170196

Informations de copyright

Copyright © 2019 Elsevier Inc. All rights reserved.

Auteurs

Carolyn F Deacon (CF)

Department of Biomedical Sciences, University of Copenhagen, Panum Institute, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark. Electronic address: deacon@sund.ku.dk.

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Classifications MeSH