Increased Neuropeptide Y Concentrations in Specific Hypothalamic Regions of Streptozocin-Induced Diabetic Rats

Abstract

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 less than .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.

C-peptide stimulates rat renal tubular Na+, K+-ATPase activity in synergism with neuropeptide Y

“…NPY is released following activation of sympathetic nerves and has been reported to act synergistically with several hormones, such as norepinephrine, angiotensin ]I and histamine [35][36][37][38]. Tissue levels of NPY are up-regulated in streptozotocintreated and C-peptide-deficient rats [23,24]. The present results suggest that the effects of C-peptide may be dependent on the activity of the sympathetic nervous system.…”

“…Insulin is of obvious importance in this context. NPY was selected, because destruction of the proinsulinproducing pancreatic beta cells may result in upregulation of NPY in many organs [23,24]. Both NPY and insulin by themselves stimulate renal tubular Na +, K +-ATPase activity depending on the concentrations [11,12].…”

Neuropeptide Y secretion increases in the paraventricular nucleus in association with increased appetite for food.

“…Since the structure of NPY is highly conserved in vertebrates (2, 26) and it induces similar robust feeding in other species (1, 4), a universal physiological role of NPY within the neural network that regulates ingestive behavior in vertebrates is possible. Furthermore, experimental hyperphagia in diabetic rats is also associated with a general activation of hypothalamic NPYergic neurons (27)(28)(29), and concentrations ofNPY are significantly altered in the CSF of patients with eating disorders (30). It is, therefore, possible that abnormal shifts in either secretion or expression of NPY action selectively at discrete anatomical substrates in the brain, which include the PVN, underlie the etiology of clinical eating disorders-namely, anorexia nervosa, bulimia, and obesity.…”

The NPY/AgRP neuron and energy homeostasis

“…NPY gene expression is upregulated during periods of negative energy balance such as fasting, 42 insulin dependent diabetes induced in rats by the b-cell toxin, streptozotocin (STZ) 43 and lactation. 44 A role for NPY in the hyperphagic response exhibited during these conditions can therefore be considered.…”