Fig. 3.

Activation of CRFR1 activates the MAPK signaling cascade and induces proliferation in rat neonatal β cells. Stimulation of CRFR1 dose-dependently increases phosphorylation of Erk1/2, an increase that is inhibited by coadministration of antalarmin (A). The induction of pErk1/2 is rapid (5 min) and persists for at least 3 h (B). oCRF and exendin-4 synergize with glucose (C). Isolated primary rat islets respond to the CRFR1-selective agonist oCRF with increased levels of pErk1/2 (D). Stimulation of rat neonatal islet cells with r/hCRF increased the nuclear incorporation of EdU into insulin-positive cells; this incorporation was blocked by antalarmin (E–G). Proliferation was quantified as the fraction of EdU insulin-positive cells (H). Numbers indicate the total number of insulin-positive cells; the number of insulin-positive EdU cells is given in parentheses. The total number of islets isolated from CRFR1-null pancreata was markedly lower than in control animals (I).