title: Does epigenetic dysregulation of pancreatic islets contribute to impaired insulin secretion and type 2 diabetes?
abstract: β cell dysfunction is central to the development and progression of type 2 diabetes (T2D). T2D develops when β cells are not able to compensate for the increasing demand for insulin caused by insulin resistance. Epigenetic modifications play an important role in establishing and maintaining β cell identity and function in physiological conditions. On the other hand, epigenetic dysregulation can cause a loss of β cell identity, which is characterized by reduced expression of genes that are important for β cell function, ectopic expression of genes that are not supposed to be expressed in β cells, and loss of genetic imprinting. Consequently, this may lead to β cell dysfunction and impaired insulin secretion. Risk factors that can cause epigenetic dysregulation include parental obesity, an adverse intrauterine environment, hyperglycemia, lipotoxicity, aging, physical inactivity, and mitochondrial dysfunction. These risk factors can affect the epigenome at different time points throughout the lifetime of an individual and even before an individual is conceived. The plasticity of the epigenome enables it to change in response to environmental factors such as diet and exercise, and also makes the epigenome a good target for epigenetic drugs that may be used to enhance insulin secretion and potentially treat diabetes.
authors.affiliation: Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Jan Waldenströms gata 35, CRC 91:12, 205 02 Malmö, Sweden.|Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Jan Waldenströms gata 35, CRC 91:12, 205 02 Malmö, Sweden.
authors.forename: Tasnim
authors.initials: T
authors.lastname: Dayeh
authors.affiliation: Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Jan Waldenströms gata 35, CRC 91:12, 205 02 Malmö, Sweden.|Epigenetics and Diabetes Unit, Department of Clinical Sciences, Lund University Diabetes Centre, Jan Waldenströms gata 35, CRC 91:12, 205 02 Malmö, Sweden.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Ling
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D044127:Epigenesis, Genetic; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology*
chemical_list: D007328:Insulin
keywords: DNA methylation; aging; chromatin; chromatine; empreinte; environnement intra-utérin; epigenetics; expression génique; gene expression; genetics; génétique; histone modifications; hyperglycemia; hyperglycémie; identité des cellules bêta; ilots pancréatiques; imprinting; insulin secretion; intrauterine environment; lipotoxicity; lipotoxicité; mitochondria; mitochondrie; modification d’histones; méthylation d’ADN; pancreatic islets; periconception; péri-conception; sécrétion d’insuline; vieillissement; épigénétique; β cell identity