| First Author | Modi H | Year | 2015 |
| Journal | Diabetes | Volume | 64 |
| Issue | 12 | Pages | 4148-57 |
| PubMed ID | 26384384 | Mgi Jnum | J:246167 |
| Mgi Id | MGI:5923698 | Doi | 10.2337/db14-1735 |
| Citation | Modi H, et al. (2015) Autocrine Action of IGF2 Regulates Adult beta-Cell Mass and Function. Diabetes 64(12):4148-57 |
| abstractText | Insulin-like growth factor 2 (IGF2), produced and secreted by adult beta-cells, functions as an autocrine activator of the beta-cell insulin-like growth factor 1 receptor signaling pathway. Whether this autocrine activity of IGF2 plays a physiological role in beta-cell and whole-body physiology is not known. Here, we studied mice with beta-cell-specific inactivation of Igf2 (betaIGF2KO mice) and assessed beta-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 betaIGF2KO mice; glucose tolerance was, however, normal because of increased insulin sensitivity. While on a high-fat diet, both male and female betaIGF2KO mice displayed lower GSIS compared with control mice, but reduced beta-cell mass was observed only in female betaIGF2KO mice. During pregnancy, there was no increase in beta-cell proliferation and mass in betaIGF2KO mice. Finally, beta-cell mass expansion in response to acute induction of insulin resistance was lower in betaIGF2KO mice than in control mice. Thus, the autocrine action of IGF2 regulates adult beta-cell mass and function to preserve in vivo GSIS in aging and to adapt beta-cell mass in response to metabolic stress, pregnancy hormones, and acute induction of insulin resistance. |
