LDHA is enriched in human islet alpha cells and upregulated in type 2 diabetes
| العنوان: | LDHA is enriched in human islet alpha cells and upregulated in type 2 diabetes |
|---|---|
| المؤلفون: | Anne Wojtusciszyn, Eva Gatineau, Blaz Lupse, Amin Ardestani, Huan Liu, Paulina Karen Mendoza Sanchez, Patrick Gilon, Ralf Dringen, Mona Khazaei, Shirin Geravandi, Kathrin Maedler |
| المساهمون: | UCL - SSS/IREC/EDIN - Pôle d'endocrinologie, diabète et nutrition |
| المصدر: | Biochemical and biophysical research communications, Vol. 568, p. 158-166 (2021) Biochem Biophys Res Commun |
| بيانات النشر: | Elsevier, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | medicine.medical_specialty, endocrine system, LDH, medicine.medical_treatment, Biophysics, Biochemistry, Glucagon, Article, LDHA, chemistry.chemical_compound, Downregulation and upregulation, Lactate dehydrogenase, Internal medicine, Insulin Secretion, medicine, Humans, Secretion, RNA, Messenger, Molecular Biology, Cells, Cultured, geography, geography.geographical_feature_category, L-Lactate Dehydrogenase, Chemistry, Pancreatic islets, Insulin, Beta-cell, Diabetes, Cell Biology, Islet, Up-Regulation, Endocrinology, medicine.anatomical_structure, Glucose, Diabetes Mellitus, Type 2, Glucagon-Secreting Cells, Lactate, Beta cell, Islets |
| الوصف: | 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. |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::38a6770995f7d59278ddba34b9970f8d https://hdl.handle.net/2078.1/249232 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....38a6770995f7d59278ddba34b9970f8d |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |