title: Defective insulin secretion in pancreatic beta cells lacking type 1 IGF receptor.
abstract: Defective insulin secretion is a feature of type 2 diabetes that results from inadequate compensatory increase of beta cell mass and impaired glucose-dependent insulin release. beta cell proliferation and secretion are thought to be regulated by signaling through receptor tyrosine kinases. In this regard, we sought to examine the potential proliferative and/or antiapoptotic role of IGFs in beta cells by tissue-specific conditional mutagenesis ablating type 1 IGF receptor (IGF1R) signaling. Unexpectedly, lack of functional IGF1R did not affect beta cell mass, but resulted in age-dependent impairment of glucose tolerance, associated with a decrease of glucose- and arginine-dependent insulin release. These observations reveal a requirement of IGF1R-mediated signaling for insulin secretion.
authors.affiliation: Department of Genetics and Development, College of Physicians & Surgeons, Columbia University, New York, New York, USA.
authors.forename: Shouhong
authors.initials: S
authors.lastname: Xuan
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Kitamura
authors.forename: Jun
authors.initials: J
authors.lastname: Nakae
authors.forename: Katerina
authors.initials: K
authors.lastname: Politi
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kido
authors.forename: Peter E
authors.initials: PE
authors.lastname: Fisher
authors.forename: Manrico
authors.initials: M
authors.lastname: Morroni
authors.forename: Saverio
authors.initials: S
authors.lastname: Cinti
authors.forename: Morris F
authors.initials: MF
authors.lastname: White
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Herrera
authors.forename: Domenico
authors.initials: D
authors.lastname: Accili
authors.forename: Argiris
authors.initials: A
authors.lastname: Efstratiadis
mesh_terms: D000818:Animals; D005089:Exocytosis; D051273:Glucose Transporter Type 2; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000032:analysis; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D017526:Receptor, IGF Type 1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D051273:Glucose Transporter Type 2; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; D017526:Receptor, IGF Type 1