The role of GIP in α-cells and glucagon secretion.
Alpha cell
Diabetes
Glucose-dependent insulinotropic polypeptide
Incretin
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:
10
09
2019
revised:
22
11
2019
accepted:
25
11
2019
pubmed:
1
12
2019
medline:
9
2
2021
entrez:
1
12
2019
Statut:
ppublish
Résumé
Glucose-dependent insulinotropic polypeptide (GIP) is an intestinally derived peptide that is secreted in response to feeding. The GIP receptor (GIPR) is expressed in many cell types involved in the regulation of metabolism, including α- and β-cells. Glucagon and insulin exert tremendous control over glucose metabolism. Thus, GIP action in islets strongly dictates metabolic control in the postprandial state. Loss of GIPR activity in β-cells is a characteristic of type 2 diabetes (T2D) which associates with reduced postprandial insulin secretion and hyperglycemia. Less is known about GIPR activity in α-cells or the control of glucagon secretion. GIP stimulates glucagon secretion in a glucose-dependent manner in healthy people, with enhanced activity at lower glycemia. However, GIP stimulates glucagon secretion even at hyperglycemia in people with T2D, suggesting that inappropriate GIPR activity in α-cells contributes to the pathogenesis of T2D. Here, we review the literature describing GIP action and GIPR activity in the α-cell, detailing the basic science that has shaped the view of how GIP regulates glucagon secretion. We also contrast the effects of GIP on glucagon secretion in healthy and T2D people. Finally, we contextualize these observations in light of recent work that redefines the role of glucagon in glucose homeostasis, suggesting that hyperglucagonemia per se does not drive hyperglycemia. As new medications for T2D that incorporate GIPR activity are being developed, it is clear that a better understanding of GIPR activity beyond the β-cell is necessary. This work highlights the importance of focusing on the GIPR in α-cells.
Identifiants
pubmed: 31785304
pii: S0196-9781(19)30191-3
doi: 10.1016/j.peptides.2019.170213
pmc: PMC7580028
mid: NIHMS1546575
pii:
doi:
Substances chimiques
Gastrointestinal Agents
0
Receptors, Gastrointestinal Hormone
0
Gastric Inhibitory Polypeptide
59392-49-3
Glucagon
9007-92-5
gastric inhibitory polypeptide receptor
D6H00MV7K8
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
170213Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK123075
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK125353
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK007012
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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