Autocrine Action of IGF2 Regulates Adult β-Cell Mass and Function
|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||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|
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|Research group||Mécanismes moléculaires et génétiques du développement sexuel (778)|
|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|