Ldha Is Enriched in Human Islet Alpha Cells and Upregulated in Type 2 Diabetes

Ldha Is Enriched in Human Islet Alpha Cells and Upregulated in Type 2 Diabetes Publisher Pubmed

Sanchez PKM¹ ; Khazaei M¹ ; Gatineau E² ; Geravandi S¹ ; Lupse B¹ ; Liu H¹ ; Dringen R¹ ; Wojtusciszyn A³ ; Gilon P² ; Maedler K¹ ; Ardestani A^{1, 4}

Show Affiliations

1. Centre for Biomolecular Interactions Bremen, University of Bremen, Bremen, Germany
2. Pole of Endocrinology, Diabetes, and Nutrition (EDIN), Institute of Experimental and Clinical Research (IREC), Universite Catholique de Louvain (UCLouvain), Brussels, 1200, Belgium
3. Department of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital, Lausanne, Switzerland
4. Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran

Source: Biochemical and Biophysical Research Communications Published:2021

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. © 2021 The Authors

2. The Hippo Kinase Lats2 Impairs Pancreatic Β-Cell Survival in Diabetes Through the Mtorc1-Autophagy Axis, Nature Communications (2021)

Experts (# of related papers)

Zahra Azizi Varzaneh (2)

Style	Citing Format
MLA	Sanchez PKM, et al.. "Ldha Is Enriched in Human Islet Alpha Cells and Upregulated in Type 2 Diabetes." Biochemical and Biophysical Research Communications, vol. 568, no. , 2021, pp. 158-166.
APA	Sanchez PKM, Khazaei M, Gatineau E, Geravandi S, Lupse B, Liu H, Dringen R, Wojtusciszyn A, Gilon P, Maedler K, Ardestani A (2021). Ldha Is Enriched in Human Islet Alpha Cells and Upregulated in Type 2 Diabetes. Biochemical and Biophysical Research Communications, 568(), 158-166.
Chicago	Sanchez PKM, Khazaei M, Gatineau E, Geravandi S, Lupse B, Liu H, Dringen R, et al.. "Ldha Is Enriched in Human Islet Alpha Cells and Upregulated in Type 2 Diabetes." Biochemical and Biophysical Research Communications 568, no. (2021): 158-166.
Harvard	Sanchez PKM et al. (2021) 'Ldha Is Enriched in Human Islet Alpha Cells and Upregulated in Type 2 Diabetes', Biochemical and Biophysical Research Communications, 568(), pp. 158-166.
Vancouver	Sanchez PKM, Khazaei M, Gatineau E, Geravandi S, Lupse B, Liu H, et al.. Ldha Is Enriched in Human Islet Alpha Cells and Upregulated in Type 2 Diabetes. Biochemical and Biophysical Research Communications. 2021;568():158-166.
BibTex	@article{ author = {Sanchez PKM and Khazaei M and Gatineau E and Geravandi S and Lupse B and Liu H and Dringen R and Wojtusciszyn A and Gilon P and Maedler K and Ardestani A}, title = {Ldha Is Enriched in Human Islet Alpha Cells and Upregulated in Type 2 Diabetes}, journal = {Biochemical and Biophysical Research Communications}, volume = {568}, number = {}, pages = {158-166}, year = {2021} }
RIS	TY - JOUR AU - Sanchez PKM AU - Khazaei M AU - Gatineau E AU - Geravandi S AU - Lupse B AU - Liu H AU - Dringen R AU - Wojtusciszyn A AU - Gilon P AU - Maedler K AU - Ardestani A TI - Ldha Is Enriched in Human Islet Alpha Cells and Upregulated in Type 2 Diabetes JO - Biochemical and Biophysical Research Communications VL - 568 IS - SP - 158 EP - 166 PY - 2021 ER -

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