Glutathione prevents chronic oscillating glucose intake-induced β-cell dedifferentiation and failure
| Autor: | Guilian Sheng, Gaoxiong Yang, Shengwei Jin, Xiufang Chen, Yanqin Li, Saijing Chen, Ming Li, Chuanzan Zhou, Hui An, Mengzhen Xie, Kaidi Ni, Tong Zhou, Jitai Zhang, Gaojun Wu, Hui Li, Bin Chen |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Blood Glucose Cancer Research medicine.medical_specialty medicine.medical_treatment Immunology 030209 endocrinology & metabolism FOXO1 Apoptosis Cell Cycle Proteins Nerve Tissue Proteins Carbohydrate metabolism Hypoinsulinemia Antioxidants Article Prediabetic State Rats Sprague-Dawley 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Internal medicine Diabetes mellitus Insulin-Secreting Cells Glucose Intolerance medicine Animals Insulin Prediabetes lcsh:QH573-671 Pancreas Glycemic business.industry lcsh:Cytology Superoxide Dismutase Cell Biology Cell Dedifferentiation medicine.disease Glutathione Rats 030104 developmental biology Endocrinology Glycemic index Glucose Female business Reactive Oxygen Species |
| Zdroj: | Cell Death & Disease Cell Death and Disease, Vol 10, Iss 4, Pp 1-13 (2019) |
| ISSN: | 2041-4889 |
| Popis: | Modern lifestyles have altered diet and metabolic homeostasis, with increased sugar intake, glycemic index, and prediabetes. A strong positive correlation between sugar consumption and diabetic incidence is revealed, but the underlying mechanisms remain obscure. Here we show that oral intake of long-term oscillating glucose (LOsG) (4 times/day) for 38 days, which produces physiological glycemic variability in rats, can lead to β-cells gaining metabolic memory in reactive oxygen species (ROS) stress. This stress leads to suppression of forkhead box O1 (FoxO1) signaling and subsequent upregulation of thioredoxin interacting protein, inhibition of insulin and SOD-2 expression, re-expression of Neurog3, and β-cell dedifferentiation and functional failure. LOsG-treated animals develop prediabetes exhibiting hypoinsulinemia and glucose intolerance. Dynamic and timely administration of antioxidant glutathione prevents LOsG/ROS-induced β-cell failure and prediabetes. We propose that ROS stress is the initial step in LOsG-inducing prediabetes. Manipulating glutathione-related pathways may offer novel options for preventing the occurrence and development of diabetes. |
| Databáze: | OpenAIRE |
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