title: Disallowed and Allowed Gene Expression: Two Faces of Mature Islet Beta Cells.
abstract: Glucose homeostasis greatly depends on the match between fluctuating insulin demands and adjusted rates of insulin secretion, which is the function of pancreatic beta cells. Emerging evidence suggests that when neonatal beta cells mature, they acquire two faces of differentiated function: an expected "visible face" that depends on specific beta cell proteins needed for regulated insulin release, but also a "hidden face" that represses ubiquitous proteins to prevent inappropriate beta cell function such as elevated basal hormone secretion or insulin release triggered by exercise. This review highlights this novel concept, and we first propose that hidden faces may also be relevant for other specialized tissue functions, such as ketogenesis in the liver. Next, we discuss three scenarios in which aberrant gene expression causes abnormal glucose-induced insulin release and the epigenetic regulation of the hidden face in beta cells. We conclude with perspectives for new research, including beta cell replacement to cure diabetes.
authors.forename: Katleen
authors.initials: K
authors.lastname: Lemaire
authors.affiliation: Gene Expression Unit, Department of Cellular and Molecular Medicine, Faculty of Medicine, KU Leuven, Leuven B3000, Belgium; email: katleen.lemaire@kuleuven.be , lieven.thorrez@kuleuven.be , frans.schuit@kuleuven.be.
authors.forename: Lieven
authors.initials: L
authors.lastname: Thorrez
authors.affiliation: Gene Expression Unit, Department of Cellular and Molecular Medicine, Faculty of Medicine, KU Leuven, Leuven B3000, Belgium; email: katleen.lemaire@kuleuven.be , lieven.thorrez@kuleuven.be , frans.schuit@kuleuven.be.
authors.forename: Frans
authors.initials: F
authors.lastname: Schuit
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation; D003920:Diabetes Mellitus / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D044127:Epigenesis, Genetic; D019317:Evidence-Based Medicine; D005786:Gene Expression Regulation; D005934:Glucagon / Q000235:genetics / Q000378:metabolism; D050416:Glucagon-Secreting Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007231:Infant, Newborn; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D016381:Islets of Langerhans Transplantation / Q000379:methods / Q000639:trends; D008954:Models, Biological; D009928:Organ Specificity; D010179:Pancreas / Q000166:cytology / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology
chemical_list: D007328:Insulin; D005934:Glucagon
keywords: chronic metabolic disease; diabetes; disallowed genes; epigenetic; insulin; repressed genes