Figure 6.
Conflicting Temporal Cues Impair Circadian Fidelity In Vitro and In Vivo
(A) Proposed mechanism by which insulin induces PER expression.
(B) Temporal relationship between glucocorticoid (corticosterone) and insulin profiles in vivo compared to in vitro assays.
(C–E) Insulin added 6 h before (orange), 6 h after (black), or at the same time as (purple) corticosterone (C) significantly affects (D) PER2 induction and (E) subsequent PER2::LUC amplitude (red: insulin alone, blue: cort alone). Grey boxes and inset in (C) show peak used for quantification (n ≥ 3, OWA, Tukey’s MCT, see also Figure S7).
(F) Bioluminescence from PER2::LUC mice i.p. injected with insulin:glucose (1.0 IU/kg:1.3 g/kg or 2.25 IU/kg:3 g/kg) during the inactive phase (n ≥ 3).
(G and H) Both doses increased PER2::LUC (G) (OWA, Dunnett’s MCT) and higher doses significantly decreased the amplitude of next circadian cycle (H). (OWA, Tukey’s MCT).
(I) Both doses reduced the robustness of PER2::LUC rhythms after injection, assessed by cosinor goodness of fit, 36 h prior to and following treatment (R2 for replicates shown, TWA, Sidak MCT). Mean ± SEM shown.