Activation of the HIF1α/PFKFB3 stress response pathway in beta cells in type 1 diabetes
| العنوان: | Activation of the HIF1α/PFKFB3 stress response pathway in beta cells in type 1 diabetes |
|---|---|
| المؤلفون: | Giovanni Coppola, Allison E. Furterer, Hiroshi Nomoto, Chiara Montemurro, Brian B. Nadel, Peter C. Butler, Tatyana Gurlo, Madeline Rosenberger, Lina Pei, Matteo Pellegrini, Slavica Tudzarova |
| المصدر: | Diabetologia, vol 63, iss 1 Diabetologia |
| بيانات النشر: | eScholarship, University of California, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Phosphofructokinase-2, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Type 2 diabetes, 0302 clinical medicine, PFKFB3, Insulin-Secreting Cells, 80 and over, 2.1 Biological and endogenous factors, Prediabetes, HIF1α, Aetiology, Child, Aged, 80 and over, Tumor, Blotting, Diabetes, Immunohistochemistry, Hedgehog signaling pathway, Cytokine, Type 1 diabetes, Public Health and Health Services, Cytokines, Female, Hypoxia-Inducible Factor 1, Beta cell, Western, Type 1, Signal Transduction, Adult, medicine.medical_specialty, Programmed cell death, Blotting, Western, Clinical Sciences, 030209 endocrinology & metabolism, Biology, alpha Subunit, Article, Cell Line, Paediatrics and Reproductive Medicine, 03 medical and health sciences, Young Adult, Endocrinology & Metabolism, Cell Line, Tumor, Internal medicine, Internal Medicine, medicine, Diabetes Mellitus, Animals, Humans, Immunoprecipitation, Beta (finance), HIF1 alpha, Metabolic and endocrine, Aged, Hypoxia-Inducible Factor 1, alpha Subunit, medicine.disease, Rats, Diabetes Mellitus, Type 1, 030104 developmental biology, Endocrinology |
| الوصف: | AIMS/HYPOTHESIS: The conserved hypoxia inducible factor 1 α (HIF1α) injury-response pro-survival pathway has recently been implicated in early beta cell dysfunction but slow beta cell loss in type 2 diabetes. We hypothesised that the unexplained prolonged prediabetes phase in type 1 diabetes may also be, in part, due to activation of the HIF1α signalling pathway. METHODS: RNA sequencing (RNA-Seq) data from human islets with type 1 diabetes or after cytokine exposure in vitro was evaluated for activation of HIF1α targets. This was corroborated by immunostaining human pancreases from individuals with type 1 diabetes for 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), the key effector of HIF1α-mediated metabolic remodelling, and by western blotting of islets and INS-1 832/13 cells exposed to cytokines implicated in type 1 diabetes. RESULTS: HIF1α signalling is activated (p=4.5×10(−9)) in islets from individuals with type 1 diabetes, and in human islets exposed in vitro to cytokines implicated in type 1 diabetes (p=1.1×10(−14)). Expression of PFKFB3 is increased fivefold (p |
| وصف الملف: | application/pdf |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4aa91163be5a899bc4054894542abda9Test https://escholarship.org/uc/item/3bp8j6v6Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4aa91163be5a899bc4054894542abda9 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |