Vitamin D binding protein/GC-globulin: a novel regulator of alpha cell function and glucagon secretion.
GC
GC-globulin
alpha cell
glucagon
metabolism
type 1 diabetes
type 2 diabetes
vitamin D
vitamin D-binding protein
Journal
The Journal of physiology
ISSN: 1469-7793
Titre abrégé: J Physiol
Pays: England
ID NLM: 0266262
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
received:
20
01
2021
accepted:
05
03
2021
pubmed:
16
3
2021
medline:
3
5
2022
entrez:
15
3
2021
Statut:
ppublish
Résumé
The contribution of glucagon to type 1 and type 2 diabetes has long been known, but the underlying defects in alpha cell function are not well-described. During both disease states, alpha cells respond inappropriately to stimuli, leading to dysregulated glucagon secretion, impaired glucose tolerance and hypoglycaemia. The mechanisms involved in this dysfunction are complex, but possibly include changes in alpha cell glucose-sensing, alpha cell de-differentiation, paracrine feedback, as well as alpha cell mass. However, the molecular underpinnings of alpha cell failure are still poorly understood. Recent transcriptomic analyses have identified vitamin D binding protein (DBP), encoded by GC/Gc, as an alpha cell signature gene. DBP is highly localized to the liver and alpha cells and is virtually absent from other tissues and cell types under non-pathological conditions. While the vitamin D transportation role of DBP is well characterized in the liver and circulation, its function in alpha cells remains more enigmatic. Recent work reveals that loss of DBP leads to smaller and hyperplastic alpha cells, which secrete less glucagon in response to low glucose concentration, despite vitamin D sufficiency. Alpha cells lacking DBP display impaired Ca
Substances chimiques
Actins
0
Globulins
0
Vitamin D-Binding Protein
0
Vitamin D
1406-16-2
Glucagon
9007-92-5
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1119-1133Subventions
Organisme : Medical Research Council
ID : MR/N00275X/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S025618/1
Pays : United Kingdom
Informations de copyright
© 2021 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.
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