title: MicroRNA-29a is up-regulated in beta-cells by glucose and decreases glucose-stimulated insulin secretion.
abstract: Chronically elevated levels of glucose impair pancreatic beta-cell function while inducing beta-cell proliferation. MicroRNA-29a (miR-29a) levels are increased in several tissues in diabetic animals and mediate decreased insulin-stimulated glucose-transport of adipocytes. The aim was to investigate the impact of glucose on miR-29a levels in INS-1E beta-cells and in human islets of Langerhans and furthermore to evaluate the impact of miR-29a on beta-cell function and proliferation. Increased glucose levels up-regulated miR-29a in beta-cells and human and rat islets of Langerhans. Glucose-stimulated insulin-secretion (GSIS) of INS-1E beta-cells was decreased by forced expression of miR-29a, while depletion of endogenous miR-29a improved GSIS. Over-expression of miR-29a increased INS-1E proliferation. Thus, miR-29a up-regulation is involved in glucose-induced proliferation of beta-cells. Furthermore, as depletion of miR-29a improves beta-cell function, miR-29a is a mediator of glucose-induced beta-cell dysfunction. Glucose-induced up-regulation of miR-29a in beta-cells could be implicated in progression from impaired glucose tolerance to type 2 diabetes.
authors.affiliation: Department of Science, Systems and Models, Roskilde University, Roskilde, Denmark.
authors.forename: Annika
authors.initials: A
authors.lastname: Bagge
authors.forename: Trine R
authors.initials: TR
authors.lastname: Clausen
authors.forename: Sylvester
authors.initials: S
authors.lastname: Larsen
authors.forename: Mette
authors.initials: M
authors.lastname: Ladefoged
authors.forename: Maiken W
authors.initials: MW
authors.lastname: Rosenstierne
authors.forename: Louise
authors.initials: L
authors.lastname: Larsen
authors.forename: Ole
authors.initials: O
authors.lastname: Vang
authors.forename: Jens H
authors.initials: JH
authors.lastname: Nielsen
authors.forename: Louise T
authors.initials: LT
authors.lastname: Dalgaard
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D048429:Cell Size; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D018149:Glucose Intolerance; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D035683:MicroRNAs / Q000096:biosynthesis*; D051381:Rats; D015854:Up-Regulation
chemical_list: D007328:Insulin; C526366:MIRN29 microRNA, rat; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D005947:Glucose