Metabolism of GIP and the contribution of GIP to the glucose-lowering properties of DPP-4 inhibitors.
Dipeptidyl peptidase-4
Glucose-dependent insulinotropic polypeptide
Incretin
Peptide degradation
Therapy
Type 2 diabetes
Journal
Peptides
ISSN: 1873-5169
Titre abrégé: Peptides
Pays: United States
ID NLM: 8008690
Informations de publication
Date de publication:
03 2020
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
170196Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.