en
Scientific article
English

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

Published inDiabetes, vol. 64, no. 12, p. 4148-4157
Publication date2015
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
  • Aging
  • Allostasis
  • Animals
  • Apoptosis
  • Cell Proliferation
  • Crosses, Genetic
  • Diet, High-Fat/adverse effects
  • Female
  • Gene Expression Regulation, Developmental
  • Glucose Intolerance/etiology/metabolism/pathology
  • Insulin/secretion
  • Insulin Resistance
  • Insulin-Like Growth Factor II/genetics/metabolism
  • Insulin-Secreting Cells/cytology/pathology/secretion
  • Male
  • Mice, Knockout
  • Mice, Transgenic
  • Pregnancy
  • Receptor, IGF Type 1/agonists/genetics/metabolism
  • Sex Characteristics
  • Signal Transduction
  • Tissue Culture Techniques
Citation (ISO format)
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
Identifiers
ISSN of the journal0012-1797
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