Figure 6. ATF4 modulates glucose metabolism through regulation of osteocalcin bioactivity by favoring Esp expression in osteoblasts.
(A–C) Blood glucose, serum insulin levels, and quantification of insulin/Ki67-immunoreactive cells in islets of 2-week-old Esp+/–Atf4+/– mice. (D) Serum uncarboxylated osteocalcin levels in α1(I)Collagen-Atf4 and Atf4osb–/– mice. (E and F) Blood glucose and serum insulin levels in uncarboxylated osteocalcin-treated α1(I)Collagen-Atf4 mice. (G) GTT in uncarboxylated osteocalcin-treated α1(I)Collagen-Atf4 mice. (H) Blood glucose (percentage of DMSO-treated control) at 60 minutes after injection in warfarin-treated α1(I)Collagen-Atf4 mice and Ocn–/– mice. Analysis shows 12-week-old α1(I)Collagen-Atf4 mice in E–G. Analysis shows 24-week-old α1(I)Collagen-Atf4 mice and Ocn–/– mice in H. Error bars show mean + SEM. **P < 0.01; *P < 0.05, WT versus Esp+/–Atf4+/– or Esp–/– mice (A–C), WT versus α1(I)Collagen-Atf4 or Atf4osb–/– mice (D) WT versus α1(I)Collagen-Atf4 mice (E–G), DMSO-treated mice as control versus warfarin-treated mice (H). #P < 0.05, α1(I)Collagen-Atf4 versus osteocalcin-treated α1(I)Collagen-Atf4 mice (E–G), WT mice plus warfarin versus α1(I)Collagen-Atf4 mice plus warfarin (H).
