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Autocrine Action of IGF2 Regulates Adult β-Cell Mass and Function

Modi, Honey
Jacovetti, Cecile
Tarussio, David
Metref, Salima
Madsen, Ole D
Zhang, Fu-Ping
Rantakari, Pia
Poutanen, Matti
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Published in Diabetes. 2015, vol. 64, no. 12, p. 4148-4157
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.
Keywords AgingAllostasisAnimalsApoptosisCell ProliferationCrosses, GeneticDiet, High-Fat/adverse effectsFemaleGene Expression Regulation, DevelopmentalGlucose Intolerance/etiology/metabolism/pathologyInsulin/secretionInsulin ResistanceInsulin-Like Growth Factor II/genetics/metabolismInsulin-Secreting Cells/cytology/pathology/secretionMaleMice, KnockoutMice, TransgenicPregnancyReceptor, IGF Type 1/agonists/genetics/metabolismSex CharacteristicsSignal TransductionTissue Culture Techniques
PMID: 26384384
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Research group Mécanismes moléculaires et génétiques du développement sexuel (778)
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MODI, Honey et al. Autocrine Action of IGF2 Regulates Adult β-Cell Mass and Function. In: Diabetes, 2015, vol. 64, n° 12, p. 4148-4157. doi: 10.2337/db14-1735 https://archive-ouverte.unige.ch/unige:86823

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Deposited on : 2016-09-06

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