title: Altered function of insulin receptor substrate-1-deficient mouse islets and cultured beta-cell lines.
abstract: Insulin receptor substrate-1 (IRS-1) is pivotal in mediating the actions of insulin and growth factors in most tissues of the body, but its role in insulin-producing beta islet cells is unclear. Freshly isolated islets from IRS-1 knockout mice and SV40-transformed IRS-1-deficient beta-cell lines exhibit marked insulin secretory defects in response to glucose and arginine. Furthermore, insulin expression is reduced by about 2-fold in the IRS-1-null islets and beta-cell lines, and this defect can be partially restored by transfecting the cells with IRS-1. These data provide evidence for an important role of IRS-1 in islet function and provide a novel functional link between the insulin signaling and insulin secretion pathways. This article may have been published online in advance of the print edition. The date of publication is available from the JCI website, http://www.jci.org.
authors.affiliation: Division of Cellular and Molecular Physiology, Research Division, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: R N
authors.initials: RN
authors.lastname: Kulkarni
authors.forename: J N
authors.initials: JN
authors.lastname: Winnay
authors.forename: M
authors.initials: M
authors.lastname: Daniels
authors.forename: J C
authors.initials: JC
authors.lastname: Brüning
authors.forename: S N
authors.initials: SN
authors.lastname: Flier
authors.forename: D
authors.initials: D
authors.lastname: Hanahan
authors.forename: C R
authors.initials: CR
authors.lastname: Kahn
mesh_terms: D000818:Animals; D002460:Cell Line; D005934:Glucagon / Q000378:metabolism; D007328:Insulin / Q000032:analysis / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000737:chemistry / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000032:analysis / Q000172:deficiency / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D010750:Phosphoproteins; D005934:Glucagon