Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuropeptide Y (NPY) injected into the hypothalamus stimulates feeding and affects pituitary secretion. Insulin-deficient diabetes and food deprivation markedly increase hypothalamic NPY and NPY mRNA levels, suggesting increased activity of NPYergic pathways in the hypothalamus, which could account for hyperphagia and neuroendocrine changes in these conditions. To clarify these changes, NPY receptor characteristics were compared amongst rats with 3-weeks' untreated streptozotocin diabetes, insulin-treated normoglycemic diabetics, and non-diabetics, and also in food-deprived (72 h), food-deprived then refed, and in freely fed rats. Hypothalamic tissue homogenates (pooled from 3 rats; n = 9 per group) in Tris/HCl buffer were incubated with 30 pM [125I]porcine NPY and unlabeled NPY (range, 1 pM to 1 microM) for 1 h. Bound and free fractions were separated by vacuum filtration. Scatchard analysis revealed both high-affinity (Kd 0.3-0.8 nM) and low-affinity (Kd 14-40 nM) NPY receptor populations. Compared with nondiabetics, diabetic rats showed significantly reduced numbers (Bmax) of both high-affinity receptors (10 +/- 2 vs. 57 +/- 2 pmol/mg protein; p < 0.001) and low-affinity receptors (113 +/- 25 vs. 544 +/- 48 pmol/mg protein; p < 0.001). Insulin treatment partially restored Bmax of both high- and low-affinity receptors (24 +/- 1 and 334 +/- 60 pmol/mg protein, respectively; p < 0.01 vs. both other groups). Food deprivation also reduced Bmax of high-affinity (36 +/- 2 vs. 56 +/- 7 pmol/mg protein in freely fed; p < 0.05) and low-affinity receptors (288 +/- 6 vs. 457 +/- 17 pmol/mg protein; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neuropeptide Y receptor numbers are reduced in the hypothalamus of streptozotocin-diabetic and food-deprived rats: further evidence of increased activity of hypothalamic NPY-containing pathways. 828 70

Levels of neuropeptide Y and neuropeptide Y mRNA are increased in the arcuate nucleus of severely diabetic rats which may be the result of the associated marked hypoinsulinaemia. We hypothesised that if neuropeptide Y mRNA is regulated by physiological changes in circulating insulin, then the relatively minor changes in circulating insulin found in mild diabetes would also affect neuropeptide Y expression and its response to changing insulin levels should be rapid. Neuropeptide Y mRNA was quantified by in situ hybridisation through the rostral, mid and caudal levels of the arcuate nucleus of adult female rats. Neuropeptide Y mRNA was significantly increased at all three levels of the arcuate nucleus, 7 days after i.v. administration of 40 mg/kg streptozotocin. Neuropeptide Y mRNA was not further increased in the arcuate nucleus of animals given 50 mg/kg streptozotocin. In the former group, serum glucose was increased but insulin levels and body weights were the same as in control rats. In the 50 mg/kg streptozotocin group, serum glucose was further increased while serum insulin and body weight were reduced. In addition, neuropeptide Y mRNA was not altered in the hypothalamic dorsomedial nucleus or the thalamic reticular nucleus. When diabetic rats were treated for 20 h with s.c. insulin, there was decreased neuropeptide Y mRNA in the arcuate nucleus. We conclude that neuropeptide Y mRNA in the arcuate nucleus is responsive to small changes in circulating insulin levels and the response occurs within 20 h. These data support that circulating insulin may contribute to control of neuropeptide Y expression under physiological conditions.
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PMID:Effects of streptozotocin-induced diabetes mellitus and insulin treatment on neuropeptide Y mRNA in the rat hypothalamus. 833 71

Neuropeptide Y (NPY) is known to be involved in the central regulation of appetite, sexual behavior, and reproductive function. Whereas central administration of NPY strongly stimulates feeding in satiated animals, diet restriction or other unfavorable metabolic situations, such as diabetes, produce enhanced NPY gene expression and NPY release in the hypothalamus. Numerous studies have indicated that acute central administration of NPY results in various actions on LH secretion in the rat, either stimulatory or inhibitory. We recently demonstrated that chronic infusion of NPY into the lateral ventricle of adult intact female rats profoundly inhibited both the gonadotropic and somatotropic axes, with disruption of estrous cyclicity. Furthermore, we showed that central chronic infusion of NPY delayed sexual maturation in female rats. To analyze the effects of the same type of chronic NPY treatment on the pituitary-testicular axis, 45-day-old Sprague-Dawley male rats were implanted with stainless steel cannulas in the right lateral ventricle. Ten days later, Alzet osmotic minipumps were filled with different NPY solutions, adjusted to deliver 6, 18, or 36 micrograms/day, connected to the intracerebroventricular (icv) cannula, and sc implanted dorsally. The effects of these treatments were evaluated over 7 days. In one case, rats were castrated 5 days after initiation of NPY treatment, and the effect of castration was evaluated 2 days later. Chronic icv infusion of NPY produced the expected dose-related increases in food intake from 33.0 +/- 0.9 (basal) to 53.4 +/- 3.3 g/day (18 micrograms NPY/day) and body weight gain (5.7 +/- 0.7 to 10.5 +/- 1.2 d/day). As in female rats, this orexigenic action of NPY resulted in a significant dose-related decrease in pituitary weight, from 12.4 +/- 0.7 to 9.9 +/- 0.4 mg. The 7-day NPY infusion produced highly significant decreases in seminal vesicle weight (853 +/- 77 to 230 +/- 31 mg) and testis weight (3.82 +/- 0.09 to 3.18 +/- 0.15 g; P = 0.003). Plasma levels of testosterone (231 +/- 71 to 48 +/- 13 ng/dl), LH (20.7 +/- 3.7 to 9.1 +/- 1.2 ng/ml), and FSH (282 +/- 17 to 190 +/- 18 ng/ml) were markedly decreased at the 18 micrograms/day dosage, as also demonstrated for the 36 micrograms/day dosage. None of these effects was observed if vehicle was infused into the lateral ventricle instead of the NPY solution. When bilateral orchidectomy was performed 5 days after initiation of the NPY infusion (18 micrograms/day), the immediate LH and FSH rises usually seen after castration were seriously blunted.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Chronic administration of neuropeptide Y into the lateral ventricle inhibits both the pituitary-testicular axis and growth hormone and insulin-like growth factor I secretion in intact adult male rats. 853 27

Neuropeptide Y is a regulatory peptide found in adrenergic and non-adrenergic neurons. Diabetes, which may cause autonomic neuropathy, induces an increase in hypothalamic neuropeptide Y (NPY) levels; thereby we measured the effects of chronic diabetes on neuropeptide Y in the intestine. Rats were injected with streptozotocin (65 mg/kg) and maintained for up to 20 weeks. Another group of rats was injected with 6-hydroxydopamine (50 mg/kg) x 2 to induce sympathectomy. Ileum and colon were harvested and both whole and microdissected intestine were (1) stained with antibodies to neuropeptide Y, vasoactive intestine polypeptide, and neurofilaments or (2) extracted for neuropeptide Y radioimmunoassay. Neuropeptide Y levels were similar under all conditions in the colon, but there was a trend toward an increase in the diabetic whole ileum. NPY levels were significantly increased in the dissected myenteric plexus ileal layer in diabetics. We noted an increase in the number of neuropeptide Y and vasoactive intestine polypeptide immunoreactive myenteric neurons in diabetics and after 6-hydroxydopamine-induced sympathectomy. Diabetes, and to a lesser extent sympathectomy, induced an increase in ileal neuropeptide Y levels and neuropeptide Y-staining myenteric but not submucosal neurons. Altered tissue levels of neuropeptide Y may account for certain of the gastrointestinal disturbances commonly seen in diabetes.
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PMID:Differential increase in neuropeptide Y-like levels and myenteric neuronal staining in diabetic rat intestine. 870 Oct 31

Neuropeptide Y (NPY) is a widely distributed neurotransmitter in the central and peripheral nervous system. In the normal rat pancreas, NPY is confined to neuronal elements, including fibers penetrating the islets. However, treatment of rats with the glucocorticoid dexamethasone (DEX) induces NPY expression also in islet cells. Previously performed double immunocytochemistry (ICC) and in situ hybridization (ISH) combined with ICC revealed that the majority of NPY-expressing islet cells are beta-cells. The present study, using ICC, ISH, and Northern blot, addressed the question whether the islet cell expression of NPY induced by DEX is affected by concomitant insulin (60 U/kg body wt daily for 12 days) treatment. Further, the time course of NPY expression in the islet cells after DEX withdrawal was examined. Treatment with DEX (2 mg/kg body wt daily for 12 days) confirmed the induction of NPY expression in numerous cells, most of which were beta-cells, dispersed within the islets. Northern blot analysis of RNA extracted from isolated islets of DEX-treated rats revealed a strong signal for NPY. Furthermore, DEX also induced NPY expression in isolated rat islets during a 5-day culture period in DEX (100 nmol/l). In vivo, the DEX-induced islet cell expression of NPY mRNA was rapidly reversed after cessation of DEX, being nondetectable 5 days post-treatment; NPY peptide was nondetectable 10 days post-treatment, indicating a slower turnover of the formed peptide. After combined treatment with DEX and insulin, the frequency of islet cells expressing NPY was markedly lower than after treatment with DEX alone. The vast majority of the NPY-expressing cells were beta-cells. In conclusion, DEX-induced NPY expression in rat islet cells is dependent on continuous DEX treatment and is partly prevented by exogenous insulin. The results suggest that the DEX-induced islet NPY expression is regulated by insulin.
Diabetes 1996 Oct
PMID:Dexamethasone-induced neuropeptide Y expression in rat islet endocrine cells. Rapid reversibility and partial prevention by insulin. 882 64

Neuropeptide Y (NPY) neurones in the arcuate nucleus of the rodent hypothalamus may play a key role in responding to reductions in body energy stores with appropriate changes in energy homeostasis, namely an increase in food-seeking behaviour and hyperphagia, together with a reduction in heat production by brown adipose tissue. These adaptive responses are mimicked by the injection of NPY into the main sites of projection of the NPY neurones, and animals that are threatened by energy deficits (e.g. through starvation or insulin-deficient diabetes) show increased activity of these neurones. Genetically obese rodents also show hyperactivity of the NPY neurones, which is inappropriate to their energy needs and may contribute to their hyperphagia, reduced energy expenditure and excessive weight gain. The NPY neurones may be inhibited by insulin and leptin, which may both serve as signals of peripheral fat mass. Ultimately, characterization of the specific "feeding' receptors which mediate NPY's central effects on energy homeostasis may provide opportunities for designing drugs to manipulate and appetite and energy balance in man, notably obesity and the cachexia commonly associated with malignancy and chronic infection.
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PMID:Neuropeptide Y, the hypothalamus and the regulation of energy homeostasis. 887 Nov 82

The obesity syndrome of ob/ob mice results from lack of leptin, a hormone released by fat cells that acts in the brain to suppress feeding and stimulate metabolism. Neuropeptide Y (NPY) is a neuromodulator implicated in the control of energy balance and is overproduced in the hypothalamus of ob/ob mice. To determine the role of NPY in the response to leptin deficiency, ob/ob mice deficient for NPY were generated. In the absence of NPY, ob/ob mice are less obese because of reduced food intake and increased energy expenditure, and are less severely affected by diabetes, sterility, and somatotropic defects. These results suggest that NPY is a central effector of leptin deficiency.
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PMID:Attenuation of the obesity syndrome of ob/ob mice by the loss of neuropeptide Y. 917 44

Neuropeptide Y (NPY) in the hypothalamus plays an important role in the regulation of food intake and body weight and seems to be implicated in the etiology of obesity. When intracerebroventricularly (ICV) infused for 6 days in normal rats, NPY resulted in hyperphagia, increased body weight gain, hyperinsulinemia, hypercorticosteronemia, and hypertriglyceridemia compared with vehicle-infused control rats. NPY infusion also resulted in an insulin-resistant state in muscles and in a state of insulin hyperresponsiveness in white adipose tissue, as assessed by the measurement of the in vivo glucose utilization index of these tissues during euglycemic-hyperinsulinemic clamps. All of these hormono-metabolic effects produced by chronic central NPY infusion were completely prevented when rats were adrenalectomized before NPY administration. Adrenalectomy per se had no effect on any of the parameters mentioned above. The levels of mRNA for the obese gene were increased in white adipose tissue after 6 days of ICV NPY infusion in normal rats, and white adipose tissue weight was also increased. These effects of ICV NPY infusion were markedly decreased by prior adrenalectomy, although NPY infusion was able to somewhat enhance the low white adipose tissue obese mRNA levels and tissue weight of adrenalectomized rats. In conclusion, intact adrenal glands, and probably circulating corticosterone in particular, are necessary for the establishment of most of the hormonal and metabolic effects induced by chronic ICV infusion of NPY in normal rats.
Diabetes 1997 Feb
PMID:Adrenalectomy prevents the obesity syndrome produced by chronic central neuropeptide Y infusion in normal rats. 900 Jun 96

Leptin acts on the brain to inhibit feeding, increase thermogenesis, and decrease body weight. Neuropeptide Y (NPY)-ergic neurons of the hypothalamic arcuate nucleus (ARC) that project to the paraventricular nuclei (PVN) and dorsomedial nuclei (DMH) are postulated to control energy balance by stimulating feeding and inhibiting thermogenesis, especially under conditions of energy deficit. We investigated whether leptin's short-term effects on energy balance are mediated by inhibition of the NPY neurons. Recombinant murine leptin (11 microg) injected into the lateral ventricle of fasted adult Wistar rats inhibited food intake by 20-25% between 2 and 6 h after administration, compared with saline-treated controls (P < 0.05). Uncoupling protein mRNA levels in brown adipose tissue (BAT) rose by 70% (P < 0.01). Leptin treatment significantly reduced NPY concentrations by 20-50% (P < 0.05) in the ARC, PVN, and DMH and significantly decreased hypothalamic NPY mRNA levels (0.61 +/- 0.02 vs. 0.78 +/- 0.03 arbitrary units; P < 0.01). A second study examined changes in leptin during 5 days' intracerebroventricular NPY administration (10 microg/day), which induced sustained hyperphagia and excessive weight gain. In NPY-treated rats, leptin mRNA levels in epididymal fat were comparable to those in saline-treated controls (0.94 +/- 0.17 vs. 1.0 +/- 0.28 arbitrary units; P > 0.1), but plasma leptin levels were significantly higher (4.88 +/- 0.66 vs. 2.85 +/- 0.20 ng/ml; P < 0.01). Leptin therefore acts centrally to decrease NPY synthesis and NPY levels in the ARC-PVN projection; reduced NPY release in the PVN may mediate leptin's hypophagic and thermogenic actions. Conversely, NPY-induced obesity results in raised circulating leptin concentrations. Leptin and the NPY-ergic ARC-PVN neurons may interact in a homeostatic loop to regulate body fat mass and energy balance.
Diabetes 1997 Mar
PMID:Interactions between leptin and hypothalamic neuropeptide Y neurons in the control of food intake and energy homeostasis in the rat. 903 86

Neuropeptide Y (NPY) is the most potent endogenous orexigenic signal. Several lines of evidence indicate that the site of NPY action in transducing feeding signal may reside in the paraventricular nucleus (PVN) and neighboring sites in the hypothalamus. To test the hypothesis that an increase in NPY activity in the ARC-PVN pathway precedes the onset of diabetic hyperphagia, we evaluated NPY levels in seven hypothalamic 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 sometimes after 48 h post-injection. These results show that augmentation in NPY neuronal activity in the ARC-PVN axis precedes the onset of increased food intake produced by STZ-induced insulinopenia. These findings affirm the hypothesis that increased NPY neurosecretion in the PVN may underlie the diabetes-induced hyperphagia.
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PMID:Evidence that hypothalamic neuropeptide Y gene expression and NPY levels in the paraventricular nucleus increase before the onset of hyperphagia in experimental diabetes. 917 3


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