Coincidence Detection Facilitates Selective PER Induction by Insulin
(A–C) IR and IGF-1R antagonist (A) BMS-754807 abolishes PER2::LUC induction (B) and phase shift (C) by insulin in fibroblasts (n = 4, TWA, Tukey’s MCT).
(D) Extracellular glucose potentiates, but is not required for, PER2::LUC induction by insulin (n = 4, TWA, Tukey’s MCT). See also Figure S6B.
(E and F) Application of MAPK pathway inhibitor U0126 does not affect PER2 induction by insulin, while inhibition of PI3K (LY294002) abolishes it (E), with quantification of induction (F) (n ≥ 3, TWA, Tukey’s MCT).
(G and H) Inhibition of mTOR (torin 1) attenuates PER2 induction by insulin (G), with quantification of induction (H) (n = 4, TWA, Tukey’s MCT).
(I and J) Simultaneous inhibition of miR24-3p, miR29a-1, and miR30a-5p with PTEN inhibition and mTOR activation recapitulates PER2::LUC induction by insulin in fibroblasts (I) (n = 4, representative, see also Figure S6K), with quantification (J) (OWA, Tukey’s MCT). Mean ± SEM for all panels except (I).
See also Figure S5.