Neuronal nitric oxide synthase in paraventricular and supraoptic hypothalamic nuclei of experimentally diabetic rats

Background and Purpose: Disturbances of the central neuroendocrine system, particularly of the hypothalamo-hypophyseal axis in diabetes mellitus have been well documented. It has been proposed that nitric oxide (NO), a signallingmolecule in the brain, might be involved in disturbances of hypothalamo-hypophyseas axis, since nitric oxide synthase (NOS) was found to be altered in certain brain areas in diabetes. Comparative studies of the hypothalamic NOS expression in two experimental models of diabetes mellitus and its time-course study have not been reported so far. Materials and Methods: By means of in situ hybridization, we have investigated the expression of neuronal NOS (nNOS) in the paraventricular (PVN) and supraoptic (SON) hypothalamic nuclei, respectively, during alloxan- and streptozotocin-induced diabetes mellitus in rats. Results: In the alloxan-induced diabetic rats, the expression of nNOS mRNA in the PVN and the SON was markedly increased, both one week (118% and 79% over control) and four weeks (92% and 78% over control) after the diabetes induction, respectively. In the streptozotocin-induced diabetic rats, only the expression of nNOS mRNA in the PVN was mildly (but statistically significantly) increased one week (+7%) and four weeks (+12%) after diabetes induction. Conclusions: The expression of hypothalamic nNOS is increased in experimentally diabetic animals, being more pronounced in the metabolically more severe, alloxan-induced diabetes mellitus. Possible implications of this alteration on regulation of glucose metabolism in the brain and/or periphery are discussed regarding NO-insulin interaction and the brain insulin system.