title: Autocrine Action of IGF2 Regulates Adult β-Cell Mass and Function.
abstract: Insulin-like growth factor 2 (IGF2), produced and secreted by adult β-cells, functions as an autocrine activator of the β-cell insulin-like growth factor 1 receptor signaling pathway. Whether this autocrine activity of IGF2 plays a physiological role in β-cell and whole-body physiology is not known. Here, we studied mice with β-cell-specific inactivation of Igf2 (βIGF2KO mice) and assessed β-cell mass and function in aging, pregnancy, and acute induction of insulin resistance. We showed that glucose-stimulated insulin secretion (GSIS) was markedly reduced in old female βIGF2KO mice; glucose tolerance was, however, normal because of increased insulin sensitivity. While on a high-fat diet, both male and female βIGF2KO mice displayed lower GSIS compared with control mice, but reduced β-cell mass was observed only in female βIGF2KO mice. During pregnancy, there was no increase in β-cell proliferation and mass in βIGF2KO mice. Finally, β-cell mass expansion in response to acute induction of insulin resistance was lower in βIGF2KO mice than in control mice. Thus, the autocrine action of IGF2 regulates adult β-cell mass and function to preserve in vivo GSIS in aging and to adapt β-cell mass in response to metabolic stress, pregnancy hormones, and acute induction of insulin resistance.
authors.affiliation: Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
authors.forename: Honey
authors.initials: H
authors.lastname: Modi
authors.affiliation: Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland.
authors.forename: Cecile
authors.initials: C
authors.lastname: Jacovetti
authors.affiliation: Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Tarussio
authors.affiliation: Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
authors.forename: Salima
authors.initials: S
authors.lastname: Metref
authors.affiliation: Hagedorn Research, Diabetes Biology, Novo Nordisk A/S, Måløv, Denmark.
authors.forename: Ole D
authors.initials: OD
authors.lastname: Madsen
authors.affiliation: Department of Physiology and Turku Center for Disease Modeling, Institute of Biomedicine, University of Turku, Turku, Finland.
authors.forename: Fu-Ping
authors.initials: FP
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Turku Center for Disease Modeling, Institute of Biomedicine, University of Turku, Turku, Finland.
authors.forename: Pia
authors.initials: P
authors.lastname: Rantakari
authors.affiliation: Department of Physiology and Turku Center for Disease Modeling, Institute of Biomedicine, University of Turku, Turku, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Poutanen
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Serge
authors.initials: S
authors.lastname: Nef
authors.affiliation: AstraZeneca, High-Content Biology, Discovery Sciences, Alderley Park, Macclesfield, Cheshire, U.K.
authors.forename: Tracy
authors.initials: T
authors.lastname: Gorman
authors.affiliation: Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland.
authors.forename: Romano
authors.initials: R
authors.lastname: Regazzi
authors.affiliation: Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland bernard.thorens@unil.ch.
authors.forename: Bernard
authors.initials: B
authors.lastname: Thorens
mesh_terms: D000375:Aging; D052636:Allostasis; D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D003433:Crosses, Genetic; D059305:Diet, High-Fat / Q000009:adverse effects; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018149:Glucose Intolerance / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011247:Pregnancy; D017526:Receptor, IGF Type 1 / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D012727:Sex Characteristics; D015398:Signal Transduction; D046509:Tissue Culture Techniques
chemical_list: C513121:IGF2 protein, mouse; D007328:Insulin; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1