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) is a powerful appetite stimulant, and hypothalamic concentrations rise after food deprivation and in experimental diabetes. Serotonergic drugs such as dexfenfluramine are inhibitors of feeding. We measured hyothalamic NPY and NPY mRNA, along with galanin, neurotensin, and somatostatin in chow-fed rats and in rats with dietary obesity, and examined the effect of dexfenfluramine on these peptides in this model. Sixty-five rats were fed a palatable diet (condensed milk, sucrose and chow) for 6 weeks, which produced significant weight gain compared to twenty fed standard chow (145.1 +/- 2.3 g vs. 113.4 +/- 3.2 g, p less than 0.001). Groups of animals were treated for 7 days or 28 days with dexfenfluramine (1.8 mg/kg/day) or saline intraperitoneally via miniosmotic pumps. Hypothalami were dissected into medial and lateral blocks, and NPY, galanin, neurotensin, and somatostatin were measured by radioimmunoassay. Neuropeptide Y mRNA was measured by Northern blotting. Hypothalamic NPY was significantly higher in the palatable diet group compared to chow-fed controls (medial hypothalamus: 86.6 +/- 7.6 vs. 65.7 +/- 4.0 pmol/g tissue, p less than 0.02, lateral hypothalamus 71.2 +/- 6.6 vs. 53.1 +/- 3.6 pmol/g tissue, p less than 0.05), but NPY mRNA was unchanged. Although dexfenfluramine was effective at reducing weight gain in the animals fed the palatable diet, this did not result in any changes in the hypothalamic neuropeptides measured. Neuropeptide Y may be of importance in diet-induced obesity but the weight loss produced by dexfenfluramine in such animals is not mediated by changes in hypothalamic NPY.
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PMID:Dexfenfluramine treatment and hypothalamic neuropeptides in diet-induced obesity in rats. 138 31

Neuropeptide Y (NPY) concentrations were measured by radioimmunoassay in eight microdissected hypothalamic regions of obese (fa/fa) and lean (Fa/?) Zucker rats. Freely fed obese rats showed significant (40-100%) increases in NPY concentrations in several regions, notably the paraventricular, ventromedial, and dorsomedial nuclei and the arcuate nucleus/median eminence, compared with lean rats. Hypothalamic NPY concentrations were not affected in either obese or lean rats by food restriction, which caused 25% weight loss over 3 wk. Refeeding to initial weight significantly increased NPY levels in the ventromedial and dorsomedial nuclei in lean rats but did not significantly alter NPY concentrations in any hypothalamic region in obese rats. These observations indicate fundamental differences in the regulation of hypothalamic NPY between obese and lean Zucker rats. NPY injected into the paraventricular nucleus and other regions causes hyperphagia, obesity, and increased secretion of insulin, glucagon, ACTH, and corticosterone. These behavioral and neuroendocrine abnormalities all occur in the obese Zucker syndrome and may be due to increased NPY-ergic activity in the hypothalamus.
Diabetes 1991 Nov
PMID:Altered neuropeptide Y concentrations in specific hypothalamic regions of obese (fa/fa) Zucker rats. Possible relationship to obesity and neuroendocrine disturbances. 165 67

Neuropeptide Y (NPY) and norepinephrine (NE) behave like cotransmitters in intrapancreatic adrenergic nerves. Therefore, in the isolated rat pancreas, we 1) studied and compared the effect of increasing concentrations of NE and NPY given alone on insulin secretion induced by 8.3 mM glucose and on pancreatic vascular flow rate and 2) investigated the effects of combinations of NPY and NE at low concentrations. NE induced a dose-dependent inhibition of insulin release between 1 and 50 nM (max 80%); beta-cells appeared sensitive to NPY at 0.1 nM, but the maximal reduction of insulin release was comparatively weak (25-30%) at 10 nM. The study of the effect of combinations of NE and NPY at different concentrations suggests that the two neurotransmitters act in an additive way to inhibit insulin secretion. NPY (0.1-10 nM) induced a marked dose-dependent reduction of pancreatic outflow rate with a biphasic pattern between 1 and 10 nM. On the other hand, at low concentrations (1 and 2 nM), NE induced a progressive increase in pancreatic outflow rate; a clear but transient decrease could only be observed at 50 nM before a secondary increase. A combined treatment with two effective concentrations of NPY (0.1 nM) and NE (1 nM) resulted in a progressive reversal by NE of NPY's vasoconstrictive effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1991 Jun
PMID:Comparison of effects of neuropeptide Y and norepinephrine on insulin secretion and vascular resistance in perfused rat pancreas. 204 Mar 81

Neuropeptide Y (NPY) concentration was determined by radioimmunoassay in selected hypothalamic regions microdissected from fresh brain slices of different types of diabetic rats. In spontaneously diabetic (BB) rats and streptozotocin (STZ)-induced diabetic rats, models of insulin-dependent diabetes mellitus, an elevated concentration of NPY was detected in the paraventricular nucleus (PVN) and arcuate nucleus (ARH) of the hypothalamus. In Wistar fatty rats, a model of non-insulin-dependent diabetes mellitus, NPY concentration was also high in the PVN as compared to controls. When STZ-induced diabetic rats were treated with insulin, elevated NPY content in the PVN returned to the normal level. These findings, together with our previous finding of increased secretion of insulin after microinjection of NPY into the PVN, suggest a crucial role of NPYergic neuronal system in the ARH-PVN area in controlling endocrine pancreas and glucose homeostasis.
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PMID:Increased neuropeptide Y content in the arcuato-paraventricular hypothalamic neuronal system in both insulin-dependent and non-insulin-dependent diabetic rats. 205 97

Neuropeptide Y (NPY) occurs within nerves in the rat pancreas, some of which are adrenergic. Therefore, we examined the influence of NPY alone and together with noradrenaline (NA) on insulin release in the rat. When infused alone for 30 min under basal conditions, NPY increased basal plasma insulin concentrations by 32 +/- 13 microU/ml at the highest dose level tested (68 pmol/min), as compared to +7 +/- 7 microU/ml in the controls (p less than 0.05). In contrast, NPY at 17 pmol/min reduced the plasma insulin response to both glucose (by 11%; p less than 0.001) and to arginine (by 26%; p less than 0.001). Infusion of NA alone (340 pmol/min) significantly elevated the basal plasma insulin levels by 41 +/- 4 microU/ml (p less than 0.001). NPY (17 pmol/min) completely abolished this effect (p less than 0.001). When NA (340 pmol/min) was added to an ongoing glucose infusion, the plasma insulin levels were markedly reduced (by 48%; p less than 0.001). By introducing NPY (17 pmol/min), this inhibitory action occurred more rapidly. However, NPY did not affect the maximal response to NA. In isolated rat islets, both NPY (10(-6) M) and NA (10(-6) M) inhibited glucose-stimulated insulin secretion. However, the maximal inhibitory effect exerted by the two neurotransmitters was not altered by giving them together. We conclude that, in the rat, NPY and NA both elevate basal plasma insulin levels and inhibit stimulated insulin secretion. In combination, NPY also induces a more rapid onset of the inhibitory action of NA on glucose-induced insulin secretion.
Diabetes Res 1990 Jan
PMID:Insulin secretion in rats: effects of neuropeptide Y and noradrenaline. 209 94

The distribution of adrenergic and vasoactive intestinal polypeptide-, neuropeptide Y- and substance P-immunoreactive nerves was studied histochemically and immunohistochemically in the irides of rats 8 weeks after the induction of diabetes with streptozotocin. In the control animals, catecholamine-containing, vasoactive intestinal polypeptide- and substance P-immunoreactive nerve fibres were found in the constrictor pupillae, dilator muscle and the ciliary processes. They also formed perivascular nerve plexuses of blood vessels in the dilator muscle. Neuropeptide Y-immunoreactive nerve fibres were only observed in the dilator muscle and ciliary processes. In the irides from diabetic animals, a considerable increase was observed in the fluorescence intensity and/or density of vasoactive intestinal polypeptide-immunoreactive nerves. Some varicosities of the vasoactive intestinal polypeptide-immunoreactive nerves appeared enlarged. In contrast, no apparent change in the density and/or fluorescence intensity of catecholamine-containing, neuropeptide Y- and substance P-immunoreactive nerve fibres was observed in the irides from diabetic animals when compared with controls. The results are discussed in relation to the symptoms of autonomic neuropathy of the irides in diabetes.
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PMID:An increase of vasoactive intestinal polypeptide-, but not neuropeptide Y-, substance P- or catecholamine-containing nerves in the iris of the streptozotocin-induced diabetic rat. 246 63

Insulin-deficient diabetes causes hypothalamic and pituitary dysfunction. The possible role of hypothalamic regulatory peptides in mediating these disturbances was investigated in spontaneously diabetic BB/E Wistar rats. Concentrations of 10 regulatory peptides were measured in the central (nucleus-rich) and lateral parts of the hypothalamus in 18 diabetic and 5 non-diabetic BB/E rats. Diabetic rats were treated with either intensified or low-dose insulin schedules to achieve moderate or severe hyperglycaemia (mean blood glucose concentrations, 8 and 20 mmol l-1 respectively). Neuropeptide Y concentration and content in the central hypothalamus were increased by 30-40% in both moderately and severely hyperglycaemic diabetic groups (p less than 0.01). Lateral hypothalamic neuropeptide Y levels did not differ significantly between the groups. The only other peptide to show any significant difference between diabetic and control rats was calcitonin gene-related peptide, whose central hypothalamic concentrations were significantly increased in the severely hyperglycaemic animals. Alterations of hypothalamic neuropeptide Y, which has potent experimental effects on hypothalamo-pituitary function, may contribute to certain neuroendocrine disturbances in insulin-deficient diabetes.
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PMID:Elevated neuropeptide Y concentrations in the central hypothalamus of the spontaneously diabetic BB/E Wistar rat. 252 1

Neuropeptide Y (NPY), a major brain neurotransmitter, is expressed in neurons of the hypothalamic arcuate nucleus (ARC) that project mainly to the paraventricular nucleus (PVN), an important site of NPY release. NPY synthesis in the ARC is thought to be regulated by several factors, notably insulin, which may exert an inhibitory action. The effects of NPY injected into the PVN and other sites include hyperphagia, reduced energy expenditure and enhanced weight gain, insulin secretion, and stimulation of corticotropin and corticosterone release. The ARC-PVN projection appears to be overactive in insulin-deficient diabetic rats, and could contribute to the compensatory hyperphagia and reduced energy expenditure, and pituitary dysfunction found in these animals; overactivity of these NPY neurons may be due to reduction of insulin's normal inhibitory effect. The ARC-PVN projection is also stimulated in rat models of obesity +/- non-insulin diabetes, possibly because the hypothalamus is resistant to inhibition by insulin; in these animals, enhanced activity of ARC NPY neurons could cause hyperphagia, reduced energy expenditure, and obesity, and perhaps contribute to hyperinsulinemia and altered pituitary secretion. Overall, these findings suggest that NPY released in the hypothalamuss, especially from the ARC-PVN projection, plays a key role in the hypothalamic regulation of energy balance and metabolism. NPY is also found in the human hypothalamus. Its roles (if any) in human homeostasis and glucoregulation remain enigmatic, but the animal studies have identified it as a potential target for new drugs to treat obesity and perhaps NIDDM.
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PMID:Neuropeptide Y, the hypothalamus, and diabetes: insights into the central control of metabolism. 747 13

It has been recently recognized that a distinct signaling pathway in the hypothalamus is involved in the stimulation of feeding in mammals. Neuropeptide Y (NPY), a member of the pancreatic polypeptide family, is the most potent orexigenic signal, and its secretion in discrete hypothalamic sites increases in response to insulinopenia produced by food deprivation or experimental diabetes. To establish the site of interaction between the hypothalamus and the pancreas, we examined the effects of insulin on NPY release in vivo and in vitro from hypothalamic sites known to be involved in feeding behavior. In the first study we evaluated the effects of peripheral insulin injections (1 U/kg.day, sc) on NPY levels in seven hypothalamic nuclei in food-deprived (FD) and ad libitum-fed rats. Whereas food deprivation for 3 days increased NPY levels in the medial preoptic area, paraventricular nucleus (PVN), and arcuate nucleus, insulin injections, which did not alter blood glucose levels, returned NPY levels to the control range selectively in the PVN. NPY levels in the hypothalamic nuclei remained unchanged after insulin injections in ad libitum-fed rats. The in vivo NPY release in the PVN of FD rats, evaluated by the push-pull cannula technique, also decreased in response to peripheral insulin injections. Finally, the effects of insulin, insulin-like growth factor I (IGF-I), and IGF-II on NPY release in vitro from the microdissected PVN and two central neighboring sites, the ventromedial nucleus and the median eminence-arcuate nucleus, of FD rats were evaluated. Both insulin (0.67 or 6.7 nM) and IGF-II (0.7 or 7.0 nM) decreased the release of NPY in a dose-dependent manner only from the PVN. On the other hand, IGF-I (0.07 or 7.0 nM) failed to alter the basal PVN NPY efflux. As the PVN is richly innervated by NPY-containing nerve terminals, the results of these in vivo and in vitro studies suggest that the site of insulin action on the hypothalamic NPY network may reside at the level of PVN nerve terminals or at the interneurons in contact with NPY nerve terminals. Although insulin may have a direct effect in reducing NPY release from the PVN, the effectiveness of IGF-II in decreasing NPY release from the PVN raises the possibility that insulin's action may also be mediated via hypothalamic IGF-II neuronal pathways.
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PMID:Insulin and insulin-like growth factor II suppress neuropeptide Y release from the nerve terminals in the paraventricular nucleus: a putative hypothalamic site for energy homeostasis. 758 28

Neuropeptides are ubiquitous in the sympathetic system and modulate transmission at the levels of the intermediolateral cell column, sympathetic ganglia, and neuroeffector junctions. Several neuropeptide-containing pathways from the hypothalamus and medulla modulate excitability of preganglionic neurons. Neuropeptides coexist with norepinephrine or acetylcholine in subpopulations of chemically coded, target-specific sympathetic ganglion neurons. Neuropeptide Y is colocalized in adrenergic vasoconstrictor neurons, whereas vasoactive intestinal polypeptide is colocalized in cholinergic sudomotor neurons. Neuropeptide expression is plastic; during development, neurons that switch from a noradrenergic to a cholinergic phenotype increase expression of vasoactive intestinal polypeptide, somatostatin, and substance P. Preganglionic inputs increase neuropeptide Y and inhibit substance P expression. Sympathetic denervation produces sprouting of sensory fibers containing substance P and calcitonin gene-related peptide in target tissues. Neuropeptides from preganglionic fibers (e.g., enkephalin) and primary afferents (e.g., substance P, vasoactive intestinal polypeptide) modulate transmission in sympathetic ganglia. Neuropeptide Y produces vasoconstriction, prejunctional inhibition of norepinephrine release, and postjunctional potentiation of norepinephrine effects. Plasma neuropeptide Y increases during intense sympathoexcitation, hypertension, and pheochromocytoma. Dystrophic neurites containing neuropeptide Y occur in human sympathetic ganglia during aging, diabetes, and dysautonomia. Sympathetic neuropeptides may thus have important clinical implications.
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PMID:Neuropeptides in the sympathetic system: presence, plasticity, modulation, and implications. 802 63


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