Untreated streptozocin-induced diabetic (STZ-D) rats have previously been shown to have significantly increased hypothalamic concentrations of neuropeptide Y (NPY), a regulatory peptide that powerfully stimulates eating and drinking and inhibits secretion of several pituitary hormones when injected centrally. Tissue NPY concentrations have been measured by radioimmunoassay in selected hypothalamic regions microdissected from fresh, unfixed brain slices to localize diabetes-associated NPY changes precisely within the hypothalamus. Significant (35–200%) increases in NPY concentrations (P < .01 vs. matched nondiabetic controls) were found in specific hypothalamic regions between 3 and 14 wk after induction of STZ-D. These regions included the paraventricular and ventromedial nuclei and lateral hypothalamic area, major appetite-regulating areas that are sensitive to the hyperphagic and polydipsic actions of NPY. Increased NPYergic activity in these areas may, at least partly, drive the increased eating and drinking characteristic of STZ-D. NPY concentrations were also increased in the arcuate nucleus and medial preoptic area. Because both of these regions are important in modulating pituitary hormone secretion, local NPY increases may be involved in the impaired secretion of luteinizing hormone, thyroid-stimulating hormone, growth hormone, and prolactin known to occur in STZ-D. Our finding of NPY increases in specific hypothalamic nuclei associated with functional changes found in STZ-D suggests that this peptide may have a role in the altered metabolic and neuroendocrine regulation of the syndrome.

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