Figure 4. Prolonged fasting promotes IGF-1/PKA dependent hematopoietic regeneration.
(A) PKA-dependent phosphorylation of CREB visualized by ICC in mouse embryonic fibroblast (MEFs) devoid of endogenous IGF-1R (R- cells) or overexpressing human IGF1R (R+ cells). R+ cells were treated with IGF-1 and compared to cells transfected with PKACα siRNA.
(B) Prolonged fasting (PF) reduces both circulating IGF-1 levels and PKA activity in BM cells in mice.
IGF-1 injection blunted the PF-induced (C) reduction of PKA/pCREB,(D) increase in hematopoietic stem cells, (E-H) The chimerism of donor-derived cells in PB and that in the BM was determined 16 weeks after primary and secondary BM transplantation.. n=4 to 8 female mice per group, * p<0.05, **p<0.01 and *** p<0.005, one-way ANOVA.