EVIDENCE THAT HYPOTHALAMIC NEUROPEPTIDE-Y GENE-EXPRESSION AND NPY LEVELS IN THE PARAVENTRICULAR NUCLEUS INCREASE BEFORE THE ONSET OF HYPERPHAGIA IN EXPERIMENTAL DIABETES

Neuropeptide Y (NPY) is the most potent endogenous orexigenic signal. Several Lines of evidence indicate that the site of NPY action in tran sducing feeding signal may reside in the paraventricular nucleus (PVN) and neighboring sites in the hypothalamus. To test the hypothesis tha t an increase in NPY activity in the ARC-PVN pathway precedes the onse t of diabetic hyperphagia, we evaluated NPY levels in seven hypothalam ic nuclei and NPY gene expression in the hypothalamus at 48, 72 or 96 h after streptozotocin (STZ) treatment in rat. In STZ-treated diabetic rats, NPY gene expression in the hypothalamus and NPY levels only in the PVN significantly elevated at 48 h, while hyperphagia occurred som etimes after 48 h post-injection. These results show that augmentation in NPY neuronal activity in the ARC-PVN axis precedes the onset of in creased food intake produced by STZ-induced insulinopenia. These findi ngs affirm the hypothesis that increased NPY neurosecretion in the PVN may underlie the diabetes-induced hyperphagia.