title: Preserved pancreatic beta-cell development and function in mice lacking the insulin receptor-related receptor.
abstract: Receptors of the insulin/insulinlike growth factor (IGF) family have been implicated in the regulation of pancreatic beta-cell growth and insulin secretion. The insulin receptor-related receptor (IRR) is an orphan receptor of the insulin receptor gene (Ir) subfamily. It is expressed at considerably higher levels in beta cells than either insulin or IGF-1 receptors, and it has been shown to engage in heterodimer formation with insulin or IGF-1 receptors. To address whether IRR plays a physiologic role in beta-cell development and regulation of insulin secretion, we have characterized mice lacking IRR and generated a combined knockout of Ir and Irr. We report that islet morphology, beta-cell mass, and secretory function are not affected in IRR-deficient mice. Moreover, lack of IRR does not impair compensatory beta-cell hyperplasia in insulin-resistant Ir(+/-) mice, nor does it affect beta-cell development and function in Ir(-/-) mice. We conclude that glucose-stimulated insulin secretion and embryonic beta-cell development occur normally in mice lacking Irr.
authors.affiliation: Naomi Berrie Diabetes Center and Department of Medicine, College of Physicians & Surgeons of Columbia University, New York, New York 10032, USA.
authors.forename: T
authors.initials: T
authors.lastname: Kitamura
authors.forename: Y
authors.initials: Y
authors.lastname: Kido
authors.forename: S
authors.initials: S
authors.lastname: Nef
authors.forename: J
authors.initials: J
authors.lastname: Merenmies
authors.forename: L F
authors.initials: LF
authors.lastname: Parada
authors.forename: D
authors.initials: D
authors.lastname: Accili
mesh_terms: D000818:Animals; D007328:Insulin / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D007515:Islets of Langerhans / Q000196:embryology / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D017526:Receptor, IGF Type 1 / Q000502:physiology; D011972:Receptor, Insulin / Q000502:physiology*
chemical_list: D007328:Insulin; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; C066542:insulin receptor-related receptor