1. Glucolipotoxicity Alters Insulin Secretion via Epigenetic Changes in Human Islets
- Author
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Jones K. Ofori, Charlotte Ling, Elin Hall, Alexander Perfilyev, Josefine Jönsson, Lena Eliasson, Marloes Dekker Nitert, Karl Bacos, and Petr Volkov
- Subjects
0301 basic medicine ,Endocrinology, Diabetes and Metabolism ,Palmitic Acid ,Gene Expression ,030209 endocrinology & metabolism ,Apoptosis ,Epigenesis, Genetic ,Transcriptome ,03 medical and health sciences ,Islets of Langerhans ,0302 clinical medicine ,Insulin-Secreting Cells ,Gene expression ,Insulin Secretion ,Internal Medicine ,medicine ,Humans ,Epigenetics ,Gene knockdown ,Chemistry ,Pancreatic islets ,Methylation ,Epigenome ,DNA Methylation ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Glucose ,DNA methylation - Abstract
Type 2 diabetes (T2D) is characterized by insufficient insulin secretion and elevated glucose levels, often in combination with high levels of circulating fatty acids. Long-term exposure to high levels of glucose or fatty acids impair insulin secretion in pancreatic islets, which could partly be due to epigenetic alterations. We studied the effects of high concentrations of glucose and palmitate combined for 48 h (glucolipotoxicity) on the transcriptome, the epigenome, and cell function in human islets. Glucolipotoxicity impaired insulin secretion, increased apoptosis, and significantly (false discovery rate
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