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)

It has been known that acupuncture has various effects such as analgesia, promotion of homeostasis, improvements in brain circulation, and rectification of internal disorders. Neuropeptide Y (NPY), a 36-amino-acid peptide, is known to increase appetite. In the present study, the effect of acupuncture stimulation at Zusanli (St.36) on NPY expression in the Streptozotocin (STZ)-induced diabetic rats was investigated via immunohistochemistry. Increased NPY expression was detected in both the Arcuate nucleus (ARN) and the Paraventricular nucleus (PVN) of the Hypothalamus in rats with in STZ-induced diabetes. Needling on Zusanli resulted in decreased NPY levels in both the ARN and PVN of diabetic rats. The present study shows that acupuncture suppressed NPY expression in the ARN and PVN of the Hypothalamus in STZ-induced diabetic rats, suggesting the possibility that acupuncture treatment is effective in curbing the hyperphagia of diabetes.
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PMID:Acupuncture decreases neuropeptide Y expression in the hypothalamus of rats with Streptozotocin-induced diabetes. 1538 90

Neuropeptide Y (NPY) has been implicated in the downstream mediation of ghrelin hyperphagia, with the site of action for both peptides considered to be intrinsic to the hypothalamus. Here, however, we observed robust hyperphagia with caudal brainstem (CBS) (fourth intracerebroventricular) ghrelin delivery and, moreover, that this response was reversed with coadministration of either of two NPY receptor antagonists (1229U91 and D-Tyr27,36, D-Thr32 NPY27-36) with contrasting NPY receptor subtype-binding properties. The same results were obtained after forebrain (third intracerebroventricular) administration, but the sites for both ghrelin and antagonist action were open to question, given the caudal flow of cerebrospinal fluid (CSF) through the ventricular system. To control for this, we occluded the cerebral aqueduct to restrict CSF flow between the forebrain and CBS ventricles and tested all combinations (same and cross ventricle) of ghrelin (150 pmol/1 microl) and NPY receptor antagonist delivery. With fourth intracerebroventricular ghrelin delivery after aqueduct occlusion, preadministration of either of the two antagonists through the same cannula reversed the hyperphagic response but neither was effective when delivered to the third ventricle. With third intracerebroventricular ghrelin administration, however, 1229U91 reversed the ingestive response only when delivered to the fourth ventricle, whereas D-Tyr27,36) D-Thr32 NPY27-36 was effective only when delivered to the forebrain. These results demonstrate distinct mediating pathways (due to location and subtypes of relevant NPY receptor) for the hyperphagic response driven separately by forebrain and CBS ghrelin administration.
Diabetes 2005 Jul
PMID:Distinct forebrain and caudal brainstem contributions to the neuropeptide Y mediation of ghrelin hyperphagia. 1598 98

An increasing number of researchers of the metabolic syndrome assume that many mechanisms are involved in its complex pathophysiology such as an increased sympathetic activity, disorders of the hypothalamo-pituitary-adrenal axis, the action of chronic subclinical infections, proinflammatory cytokines, and the effect of adipocytokines or psychoemotional stress. An increasing body of scientific research in this field confirms the role of the neurotrophins and mastocytes in the pathogenesis of inflammatory and immune diseases. Recently it has been proved that neurotrophins and mastocytes have metabotrophic effects and take part in the carbohydrate and lipid metabolism. In the early stage of the metabolic syndrome we established a statistically significant increase in the plasma levels of the nerve growth factor. In the generalized stage the plasma levels of the neutrophines were statistically decreased in comparison to those in the healthy controls. We consider that the neurotrophin deficit is likely to play a significant pathogenic role in the development of the metabolic anthropometric and vascular manifestations of the generalized stage of MetSyn. We suggest a hypothesis for the etiopathogenesis of the metabolic syndrome based on the neuro-immuno-endocrine interactions. The specific pathogenic pathways of MetSyn development include: (1) increased tissue and plasma levels of proinflammatory cytokines Interleukin-1(IL-1), Interleukin-6 (IL-6 ) and tumor necrosis factor - alpha (TNF-alpha) caused by inflammatory and/or emotional distress; (2) increased plasma levels of neurotrophin - nerve growth factor (NGF) caused by the high IL-1, IL-6 and TNFalpha levels; (3) high plasma levels of NGF which enhance activation of: the autonomous nerve system--vegetodystonia (disbalance of neurotransmitters); Neuropeptide Y (NPY)--enhanced feeding, obesity and increased leptin plasma levels; hypothalamo-pituitary-adrenal axis--increased corticotropin-releasing hormone (CRH) and cortisol (hormonal disbalance); immune cells--increased number and degranulation of mastocytes (MC)--immunological disbalance; (4) as a result of 1-3 insulin resistance is exhibited leading to diabetes mellitus. The hypothesis is confirmed by results obtained after 6-month nonsteroid anti-inflammatory treatment of patients with MetSyn. These results are reported in a separate publication.
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PMID:Metabolic syndrome--neurotrophic hypothesis. 1654 15

Neuropeptide Y receptors are critical regulators of energy homeostasis, but the functional interactions and relative contributions of Y receptors and the environment in this process are unknown. We measured the effects of an ad libitum diet of normal or high-fat food on energy balance in mice with single, double, or triple deficiencies of Y1, Y2, or Y4 receptors. Whereas wild-type mice developed diet-induced obesity, Y2Y4 double knockouts did not. In contrast, Y1 knockout or Y1Y2 or Y1Y4 receptor double knockout mice developed an exacerbated diet-induced obesity syndrome. Remarkably, the antiobesity effect of Y2Y4 deficiency was stronger than the obesogenic effect of Y1 deficiency, since Y1Y2Y4 triple knockouts did not develop obesity on the high-fat diet. Resistance to diet-induced obesity in Y2Y4 knockouts was associated with reduced food intake and improved glucose tolerance in the absence of changes in total physical activity. Fecal concentration of free fatty acids was significantly increased in Y2Y4 knockouts in association with a significantly reduced bile acid pool and marked alterations in intestinal morphology. In addition, hypothalamic proopiomelanocortin expression was decreased in diet-induced obesity (in both wild-type and Y1 receptor knockout mice) but not in obesity-resistant Y2Y4 receptor knockout mice fed a high-fat diet. Therefore, deletion of Y2 and Y4 receptors synergistically protects against diet-induced obesity, at least partially via changes in food intake and hypothalamic proopiomelanocortin expression.
Diabetes 2006 Jan
PMID:Y2Y4 receptor double knockout protects against obesity due to a high-fat diet or Y1 receptor deficiency in mice. 1638 Apr 72

The cocaine and amphetamine regulated transcript (CART), an anorexigenic peptide responding to leptin, is expressed in various areas of the hypothalamus. The role of CART in humans and its potential contribution to abnormalities in feeding control are mostly unknown. Since CART plays an important role in the hypothalamic regulation of energy balance by reducing food intake and increasing lipid substrate utilization, it might affect cholesterol metabolism as Neuropeptide Y or pro-opiomelanocortin do. In the present work, we studied the potential effects of three SNPs of the CART promoter in a WHO-MONICA general population from North of France (n=840), untreated for hypercholesterolemia, hypertension, or diabetes mellitus since any treatment is likely to interfere with lipoprotein/lipid variables. Our results show associations between these SNPs and plasma LDL-cholesterol level and the LDL/HDL ratio, a marker of atherogenicity. A haplotypic study suggests that these effects are mainly attributable to the functional SNP -3608C>T. Subjects bearing the -3608 C allele present a plasma lipid profile protective against atherogenesis: decrease of plasma LDL-cholesterol level (p=0.001) and of the LDL/HDL ratio (p=0.0003). This result offers new evidences for a potential implication of the CART gene in lipid metabolism and in atherogenesis.
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PMID:Impact of a CART promoter genetic variation on plasma lipid profile in a general population. 1700 16

Neuropeptide Y (NPY) stimulates feeding and weight gain, but deletion of the NPY gene does not affect food intake and body weight in mice bred on a mixed genetic background. We reasoned that the orexigenic action of NPY would be evident in C57Bl/6J mice susceptible to obesity. NPY deficiency has no significant effect in mice fed a normal rodent diet. However, energy expenditure is elevated during fasting, and hyperphagia and weight gain are blunted during refeeding. Expression of agouti-related peptide (AGRP) in the hypothalamus is increased in NPY knockout (NPYko) than wild-type mice, but unlike wild type there is no further increase in AGRP when NPYko mice are fasted. Moreover, NPYko mice have higher oxygen consumption and uncoupling protein-1 expression in brown adipose tissue during fasting. The failure of an increase in orexigenic peptides and higher thermogenesis may contribute to attenuation of weight gain when NPYko mice are refed. C57Bl/6J mice lacking NPY are also less susceptible to diet-induced obesity (DIO) as a result of reduced feeding and increased energy expenditure. The resistance to DIO in NPYko mice is associated with a reduction in nocturnal feeding and increased expression of anorexigenic hypothalamic peptides. Insulin, leptin, and triglyceride levels increase with adiposity in both wild-type and NPYko mice.
Diabetes 2006 Nov
PMID:Neuropeptide Y deficiency attenuates responses to fasting and high-fat diet in obesity-prone mice. 1706 47

Neuropeptide Y (NPY) is a sympathetic neurotransmitter that plays a role in e.g. circulation, hormone release and angiogenesis. Earlier studies have shown that the Leucine 7 to Proline 7 (Leu7Pro) polymorphism of preproNPY is associated with increased risk for vascular complications in type 2 diabetes. The mechanism for this maybe altered transmitter and hormone levels or altered cardiovascular functions, which have been observed in healthy subjects having the Leu7Pro polymorphism. The current study was undertaken to explore if the Leu7Pro polymorphism has an impact on these functions in subjects with type 2 diabetes. Diurnal measurements were performed for Finnish Caucasian type 2 diabetes patients of two preproNPY genotypes (matched by sex, age, BMI, duration of diabetes and HbA1c) in resting position to prevent sympathetic stimulation. Standard meals were offered during the 24-hour study period. Nine subjects with the Leu7Pro polymorphism and ten subjects without this polymorphism were studied. Plasma concentrations of NPY, glucose, insulin, cortisol, prolactin and leptin were measured by taking blood samples at 20 time points (from 8 a.m. to 8 a.m.). Heart rate and blood pressure were measured at the same time points. The results show that NPY concentrations were similar in both preproNPY genotypes. Glucose, insulin, cortisol and leptin concentrations as well as heart rate and blood pressure were also similar. However, a significant difference between genotypes was found in the association of NPY concentrations with cortisol concentrations (p for difference=0.002). Also a statistically significant negative association of plasma NPY levels with plasma glucose levels was found in both genotypes. Since no impact of preproNPY genotype on mean NPY or hormone levels were detected in subjects with type 2 diabetes, the mechanisms for the increased risk for diabetic complications in the subjects with the Leu7Pro polymorphism need to be further explored.
Exp Clin Endocrinol Diabetes 2007 May
PMID:Impact of the Leu7Pro polymorphism of preproNPY on diurnal NPY and hormone secretion in type 2 diabetes. 1751 89

Neuropeptide Y (NPY) is a universally expressed neuropeptide involved in the regulation of several physiological functions. The rather common leucine7 to proline7 (L7P) polymorphism in the signal peptide of preproNPY is a functional substitution, which changes the processing and release of NPY in cells. The mutation is associated with altered lipid levels and accelerated atherosclerosis in humans. Based on previous studies, we investigated the effect of the Pro7 allele in endothelial cells, which are known to play a role in the development of atherosclerosis. Cell proliferation and apoptosis were studied in primary cultured, genotyped human umbilical vein endothelial cells (HUVECs). Our results indicate that cells with the [p.L7]+[p.P7] genotype seem to have a tendency to be more sensitive to the growth stimulating effect of NPY and less sensitive to the effect of vascular endothelial growth factor compared to cells with the [p.L7]+[p.L7] genotype. Additionally, cells with the [p.L7]+[p.P7] genotype seem to be more sensitive to apoptosis than [p.L7]+[p.L7] cells. We speculate that the L7P substitution in preproNPY might cause a state of cellular pre-senescence, leading to endothelial dysfunction. This might be one reason for the associations of the L7P polymorphism with atherosclerosis and type II diabetes found in clinical studies.
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PMID:The effect of endogenous preproneuropeptide Y leucine 7 to proline 7 polymorphism on growth and apoptosis in primary cultured HUVECs. 1955 21

Diabetes induces changes in the structural, biochemical, electrical, and contractile properties of skeletal muscles. Neuropeptide Y (NPY) administered locally can induce angiogenesis in a rat ischemic limb model and restore the contractile function of the ischemic muscle. The effects of NPY on the contractile characteristics of limb skeletal muscles were examined in streptozotocin-induced diabetic rats. Rats were treated with sham pellets (control groups) or NPY-containing pellets (1 mg of NPY/pellet, 14 days releasing time) administered locally to the rat hind limb 2 months after induction of diabetes. Contractile properties and fatigability of the slow-twitch soleus and fast-twitch gastrocnemius medials muscle were compared in control (sham), control NPY, diabetic (sham), and diabetic NPY groups. In order to induce fatigue trains of repetitive tetanic stimulation were used (600 ms/1 s simulation-rest cycle per train, 112 trains at an 85-Hz fusion frequency). Two months of untreated diabetes significantly prolonged soleus contraction and slowed its relaxation, but had minimal effects on soleus tension. NPY ameliorated the diabetic effects on soleus speed-related contractile properties, restoring its contraction and relaxation times. Diabetes significantly reduced gastrocnemius medials tetanic tension, leaving its contractile characteristics mostly unaffected. NPY partially restored gastrocnemius tetanic tension production capacity. Diabetes significantly increased fatigability of both muscles, which was partially restored by NPY, as evidenced by restored endurance of soleus muscle. The results suggest that NPY administered locally tends to normalize muscle performance and improve fatigue resistance of skeletal muscles in streptozotocin diabetes. Further examination is needed to establish the mechanisms of local NPY action on muscle contractile properties in streptozotocin-induced diabetes.
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PMID:The effects of neuropeptide Y on skeletal muscle contractile properties in streptozotocin diabetic rats. 1961 25

Neuropeptide Y (NPY) and agouti-related protein (AgRP) have powerful stimulatory effects on food intake, which suggests that the downregulation of brain NPY or AgRP may help reduce obesity and diabetes by inhibiting food intake. To search for active compounds that inhibit NPY and AgRP expression, we made two luciferase reporter assay systems consisting of NPY and AgRP promoter-driven luciferase genes, together with the puromycin resistance gene, in a plasmid vector. Each plasmid was permanently transfected into N29-4 neuronal cells. Using the systems, resveratrol was purified from the stem of Vitis coignetiae Pulliat by activityguided fractionation. Resveratrol downregulated NPY and AgRP promoter-driven luciferase activity in a dose-dependent manner. The inhibitory concentrations (IC(50), 50% inhibition) of resveratrol against pNPY-luc and pAgRP-luc activities were 8.9 microM and 8.0 microM, respectively. Furthermore, one-time intraperitoneal injection of resveratrol (100 mg/kg) suppressed 20.0% and 17.2% of food intake during 24 and 48 h, respectively. These results indicated that resveratrol inhibited food intake, which may be related to the downregulation of NPY and AgRP gene expression.
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PMID:Resveratrol, purified from the stem of Vitis coignetiae Pulliat, inhibits food intake in C57BL/6J Mice. 2051 77


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