Leptin modulation of neuronal transcript levels was abolished after induction of insulin resistance. rHypoE-19 neurons were pretreated with either PBS or 100 nM insulin for 24 hours. The cells were then washed and allowed to recover in fresh medium for 1 hour before 10 nM leptin treatment for 1 hour (AgRP only) or 8 hours. Insulin resistance attenuates a leptin-induced decrease of AgRP (a) and increases in UCN2 (b), IRS1 (c), IRS2 (d), and IR (e) transcript levels. mRNA levels were determined by qRT-PCR and normalized to 18S rRNA and shown with SEMs (n = 3–4 independent experiments). *, P < .05; **, P < .01, vs vehicle control, as per t tests.