LDHA is enriched in human islet alpha cells and upregulated in type 2 diabetes.
Beta-cell
Diabetes
Islets
LDH
LDHA
Lactate
Journal
Biochemical and biophysical research communications
ISSN: 1090-2104
Titre abrégé: Biochem Biophys Res Commun
Pays: United States
ID NLM: 0372516
Informations de publication
Date de publication:
03 09 2021
03 09 2021
Historique:
received:
17
06
2021
accepted:
20
06
2021
pubmed:
5
7
2021
medline:
20
11
2021
entrez:
4
7
2021
Statut:
ppublish
Résumé
The lactate dehydrogenase isoform A (LDHA) is a key metabolic enzyme that preferentially catalyzes the conversion of pyruvate to lactate. Whereas LDHA is highly expressed in many tissues, its expression is turned off in the differentiated adult β-cell within the pancreatic islets. The repression of LDHA under normal physiological condition and its inappropriate upregulation under a diabetogenic environment is well-documented in rodent islets/β-cells but little is known about LDHA expression in human islet cells and whether its abundance is altered under diabetic conditions. Analysis of public single-cell RNA-seq (sc-RNA seq) data as well as cell type-specific immunolabeling of human pancreatic islets showed that LDHA was mainly localized in human α-cells while it is expressed at a very low level in β-cells. Furthermore, LDHA, both at mRNA and protein, as well as lactate production is upregulated in human pancreatic islets exposed to chronic high glucose treatment. Microscopic analysis of stressed human islets and autopsy pancreases from individuals with type 2 diabetes (T2D) showed LDHA upregulation mainly in human α-cells. Pharmacological inhibition of LDHA in isolated human islets enhanced insulin secretion under physiological conditions but did not significantly correct the deregulated secretion of insulin or glucagon under diabetic conditions.
Identifiants
pubmed: 34217973
pii: S0006-291X(21)00989-X
doi: 10.1016/j.bbrc.2021.06.065
pmc: PMC8364499
mid: NIHMS1720992
pii:
doi:
Substances chimiques
RNA, Messenger
0
L-Lactate Dehydrogenase
EC 1.1.1.27
LDHA protein, human
EC 1.1.1.27
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
158-166Subventions
Organisme : NIDDK NIH HHS
ID : U24 DK098085
Pays : United States
Organisme : NIDDK NIH HHS
ID : UC4 DK098085
Pays : United States
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare no conflict of interests.
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