Diabetes.: auth.: B.Thorens

Diabetes. 2015 Sep 17. pii: db141735. [Epub ahead of print]

Autocrine action of IGF2 regulates adult β cell mass and function.


IGF2 produced and secreted by adult β cells, functions as an autocrine activator of the β cell IGF1R 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 ageing, 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. On high fat diet, both male and female βIGF2KO mice displayed lower GSIS as compared to 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 than in control mice. Thus, the autocrine action of IGF2 regulates adult β cell mass and function to preserve in vivo GSIS in ageing, and to adapt β cell mass in response to metabolic stress, pregnancy hormones, and acutely induced insulin resistance.

© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

PMID: 26384384