LDHA is enriched in human islet alpha cells and upregulated in type 2 diabetes.

Details

Serval ID
serval:BIB_913C1F9941F9
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
LDHA is enriched in human islet alpha cells and upregulated in type 2 diabetes.
Journal
Biochemical and biophysical research communications
Author(s)
Sanchez PKM, Khazaei M., Gatineau E., Geravandi S., Lupse B., Liu H., Dringen R., Wojtusciszyn A., Gilon P., Maedler K., Ardestani A.
ISSN
1090-2104 (Electronic)
ISSN-L
0006-291X
Publication state
Published
Issued date
01/07/2021
Peer-reviewed
Oui
Volume
568
Pages
158-166
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Abstract
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.
Keywords
Beta-cell, Diabetes, Islets, LDH, LDHA, Lactate
Pubmed
Web of science
Open Access
Yes
Create date
12/07/2021 8:46
Last modification date
18/09/2021 5:38
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