title: Dysregulation of Dicer1 in beta cells impairs islet architecture and glucose metabolism.
abstract: microRNAs (miRNAs) play important roles in pancreas development and in regulation of insulin expression in the adult. Here we show that loss of miRNAs activity in beta-cells during embryonic development results in lower beta-cell mass and in impaired glucose tolerance. Dicer1-null cells initially constitute a significant portion of the total beta-cell population. However, during postnatal development, Dicer1-null cells are depleted. Furthermore, wild-type beta cells are repopulating the islets in complex compensatory dynamics. Because loss of Dicer1 is also associated with changes in the distribution of membranous E-cadherin, we hypothesized that E-cadherin activity may play a role in beta cell survival or islet architecture. However, genetic loss of E-cadherin function does not impair islet architecture, suggesting that miRNAs likely function through other or redundant effectors in the endocrine pancreas.
authors.affiliation: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Amitai D
authors.initials: AD
authors.lastname: Mandelbaum
authors.forename: Tal
authors.initials: T
authors.lastname: Melkman-Zehavi
authors.forename: Roni
authors.initials: R
authors.lastname: Oren
authors.forename: Sharon
authors.initials: S
authors.lastname: Kredo-Russo
authors.forename: Tomer
authors.initials: T
authors.lastname: Nir
authors.forename: Yuval
authors.initials: Y
authors.lastname: Dor
authors.forename: Eran
authors.initials: E
authors.lastname: Hornstein
mesh_terms: D000818:Animals; D017209:Apoptosis; D001786:Blood Glucose / Q000032:analysis; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D003433:Crosses, Genetic; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D018149:Glucose Intolerance / Q000097:blood / Q000378:metabolism* / Q000473:pathology*; D006579:Heterozygote; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology*; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D007515:Islets of Langerhans / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000378:metabolism*; D009154:Mutation; D038081:Organogenesis; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D015820:Cadherins; D007328:Insulin; D035683:MicroRNAs; C045073:Cre recombinase; D019426:Integrases; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases