Publications
179 results found
Alamshah A, Spreckley E, McGavigan AK, et al., 2014, L-Arginine Promotes Gut Hormone Release and Reduces Appetite in Rodents, ENDOCRINE REVIEWS, Vol: 35, ISSN: 0163-769X
Kinsey-Jones JS, Beale KE, Cuenco J, et al., 2014, Quantification of Rat Kisspeptin Using a Novel Radioimmunoassay, PLoS ONE, Vol: 9, ISSN: 1932-6203
Kisspeptin is a hypothalamic peptide hormone that plays a pivotal role in pubertal onset and reproductive function. Previous studies have examined hypothalamic kisspeptin mRNA expression, either through in situ hybridisation or real-time RT-PCR, as a means quantifying kisspeptin gene expression. However, mRNA expression levels are not always reflected in levels of the translated protein. Kisspeptin-immunoreactivity (IR) has been extensively examined using immunohistochemistry, enabling detection and localisation of kisspeptin perikaya in the arcuate nucleus (ARC) and anteroventral periventricular nucleus (AVPV). However, quantification of kisspeptin-IR remains challenging. We developed a specific rodent radioimmunoassay assay (RIA) capable of detecting and quantifying kisspeptin-IR in rodent tissues. The RIA uses kisspeptin-10 as a standard and radioactive tracer, combined with a commercially available antibody raised to the kisspeptin-10 fragment. Adult female wistar rat brain samples were sectioned at 300 µm and the ARC and AVPV punch micro-dissected. Brain punches were homogenised in extraction buffer and assayed with rodent kisspeptin-RIA. In accord with the pattern of kisspeptin mRNA expression, kisspeptin-IR was detected in both the ARC (47.1±6.2 fmol/punch, mean±SEM n = 15) and AVPV (7.6±1.3 fmol/punch, mean±SEM n = 15). Kisspeptin-IR was also detectable in rat placenta (1.26±0.15 fmol/mg). Reverse phase high pressure liquid chromatography analysis showed that hypothalamic kisspeptin-IR had the same elution profile as a synthetic rodent kisspeptin standard. A specific rodent kisspeptin-RIA will allow accurate quantification of kisspeptin peptide levels within specific tissues in rodent experimental models.
Basharat S, Parker JA, Murphy KG, et al., 2014, Leptin fails to blunt the lipopolysaccharide-induced activation of the hypothalamic-pituitary- adrenal axis in rats, Journal of Endocrinology, Vol: 221, Pages: 229-234, ISSN: 0022-0795
Obesity is a risk factor for sepsis morbidity and mortality, whereas the hypothalamic–pituitary–adrenal (HPA) axis plays a protective role in the body's defence against sepsis. Sepsis induces a profound systemic immune response and cytokines serve as excellent markers for sepsis as they act as mediators of the immune response. Evidence suggests that the adipokine leptin may play a pathogenic role in sepsis. Mouse endotoxaemic models present with elevated leptin levels and exogenously added leptin increased mortality whereas human septic patients have elevated circulating levels of the soluble leptin receptor (Ob-Re). Evidence suggests that leptin can inhibit the regulation of the HPA axis. Thus, leptin may suppress the HPA axis, impairing its protective role in sepsis. We hypothesised that leptin would attenuate the HPA axis response to sepsis. We investigated the direct effects of an i.p. injection of 2 mg/kg leptin on the HPA axis response to intraperitoneally injected 25 μg/kg lipopolysaccharide (LPS) in the male Wistar rat. We found that LPS potently activated the HPA axis, as shown by significantly increased plasma stress hormones, ACTH and corticosterone, and increased plasma interleukin 1β (IL1β) levels, 2 h after administration. Pre-treatment with leptin, 2 h before LPS administration, did not influence the HPA axis response to LPS. In turn, LPS did not affect plasma leptin levels. Our findings suggest that leptin does not influence HPA function or IL1β secretion in a rat model of LPS-induced sepsis, and thus that leptin is unlikely to be involved in the acute-phase endocrine response to bacterial infection in rats.
McGowan BM, Minnion JS, Murphy KG, et al., 2014, Relaxin-3 stimulates the neuro-endocrine stress axis via corticotrophin-releasing hormone, JOURNAL OF ENDOCRINOLOGY, Vol: 221, Pages: 337-346, ISSN: 0022-0795
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- Citations: 29
Agahi A, Murphy KG, 2014, Models and Strategies in the Development of Antiobesity Drugs, VETERINARY PATHOLOGY, Vol: 51, Pages: 695-706, ISSN: 0300-9858
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- Citations: 8
Beale KE, Kinsey-Jones JS, Gardiner JV, et al., 2014, The Physiological Role of Arcuate Kisspeptin Neurons in the Control of Reproductive Function in Female Rats, ENDOCRINOLOGY, Vol: 155, Pages: 1091-1098, ISSN: 0013-7227
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- Citations: 36
Chambers ES, Viardot A, Psichas A, et al., 2014, Targeted delivery of propionate to the human colon prevents body weight and intra-abdominal adipose tissue gain in overweight adults, PROCEEDINGS OF THE NUTRITION SOCIETY, Vol: 73, Pages: E22-E22, ISSN: 0029-6651
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- Citations: 1
Chambers ES, Viardot A, Psichas A, et al., 2014, Targeted delivery of propionate to the colon stimulates the release of anorectic gut hormones and suppresses appetite in humans, PROCEEDINGS OF THE NUTRITION SOCIETY, Vol: 73, Pages: E15-E15, ISSN: 0029-6651
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- Citations: 1
Boughton CK, Murphy KG, 2013, Can neuropeptides treat obesity? A review of neuropeptides and their potential role in the treatment of obesity, BRITISH JOURNAL OF PHARMACOLOGY, Vol: 170, Pages: 1333-1348, ISSN: 0007-1188
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- Citations: 27
Boughton CK, Patel SA, Thompson EL, et al., 2013, Neuromedin B stimulates the hypothalamic-pituitary-gonadal axis in male rats, REGULATORY PEPTIDES, Vol: 187, Pages: 6-11, ISSN: 0167-0115
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- Citations: 11
Sam A, Busbridge M, Amin A, et al., 2013, Hepcidin levels in diabetes mellitus and polycystic ovary syndrome, Diabetic Medicine, Vol: 30, Pages: 1495-1499, ISSN: 0742-3071
Smith S, Alexander A, Dubb S, et al., 2013, Opening doors and minds: A path for widening access, Clinical Teacher, Vol: 10, Pages: 124-128, ISSN: 1743-4971
Background: Students from disadvantaged socio-economic backgrounds are under-represented in UK medical schools. Many successful interventions are also highly labour-intensive for medical schools to implement. We describe and evaluate a sustainable, low-cost strategy that provides participants with targeted support, advice and experience. Methods: Year-12 participants (29-74 annually) from schools in areas of deprivation were paired with e-mentors from the medical student population. Engagement with this programme was used as one criterion to select approximately 20 mentees per year for participation in a 1-week summer school. All participants were offered consultant-led work experience during their summer holiday and were guaranteed places at a student-led outreach conference, where they received specific help with the writing of personal statements and interview skills. Summer school participants were followed-up by questionnaire to establish their career plans. Results: We have delivered this programme annually for 3years. All respondents to follow-up applied to study medicine, dentistry or a related bioscience, to degree level. The success rate of these disadvantaged students was similar to that of the general population of UK applicants who applied to study medicine at this medical school. Discussion: By collaboratively linking multiple activities organised by the Outreach Office, academic staff and medical students, an annual cohort of approximately 20 participants from non-traditional backgrounds was provided with sustained support in preparing for applying to medical school. The limited data available from follow-up suggests that this approach may have helped overcome the social disadvantage facing these applicants. © Blackwell Publishing Ltd 2013.
McGavigan AK, Murphy KG, 2012, Gut hormones: the future of obesity treatment?, BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Vol: 74, Pages: 911-919, ISSN: 0306-5251
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- Citations: 20
Hill NE, Murphy KG, Brett S, et al., 2012, CAN THE GASTRIC HORMONE GHRELIN ATTENUATE CATABOLISM AND ENHANCE RECOVERY AND REHABILITATION IN A RODENT MODEL OF ZYMOSAN PERITONITIS?, INTENSIVE CARE MEDICINE, Vol: 38, Pages: S122-S122, ISSN: 0342-4642
Ramachandran R, Bech P, Murphy KG, et al., 2012, Improved diagnostic accuracy for neuroendocrine neoplasms using two chromogranin A assays., Clin Endocrinol (Oxf), Vol: 76, Pages: 831-836
Chromogranin A (Cg A) is the best available diagnostic marker for neuroendocrine neoplasms (NENs). However, clinical interpretation of Cg A results may be limited by considerable heterogeneity between commonly available Cg A assays. Variation in diagnostic accuracy of these assays largely reflects differences in antibody specificities. We compared the diagnostic utility of four Cg A assays [Imperial Supra-regional Assay Service radioimmunoassay (SAS) and three commercial assays, Cisbio, DAKO and Eurodiagnostica].
Hill NE, Murphy KG, Singer M, 2012, Ghrelin, appetite and critical illness, CURRENT OPINION IN CRITICAL CARE, Vol: 18, Pages: 199-205, ISSN: 1070-5295
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- Citations: 16
Amin A, Murphy KG, 2012, Nutritional sensing and its utility in treating obesity., Expert Rev Endocrinol Metab, Vol: 7, Pages: 209-221
Obesity remains a major worldwide health problem, with current medical treatments being poorly effective. Nutrient sensing allows organs such as the GI tract and the brain to recognize and respond to fuel substrates such as carbohydrates, protein and fats. Specialized neural and hormonal pathways exist to facilitate and regulate these chemosensory mechanisms. Manipulation of factors involved in either central or peripheral chemosensory pathways may provide possible targets for the manipulation of appetite. However, further research is required to assess the utility of this approach to developing novel anti-obesity agents.
Jayasena CN, Nijher GMK, Comninos AN, et al., 2011, The Effects of Kisspeptin-10 on Reproductive Hormone Release Show Sexual Dimorphism in Humans, JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, Vol: 96, Pages: E1963-E1972, ISSN: 0021-972X
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- Citations: 89
Addison ML, Minnion JS, Shillito JC, et al., 2011, A Role for Metalloendopeptidases in the Breakdown of the Gut Hormone, PYY<sub>3-36</sub>, ENDOCRINOLOGY, Vol: 152, Pages: 4630-4640, ISSN: 0013-7227
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- Citations: 19
Beale KEL, Murphy KG, Harrison EK, et al., 2011, Accurate Measurement of Body Weight and Food Intake in Environmentally Enriched Male Wistar Rats, OBESITY, Vol: 19, Pages: 1715-1721, ISSN: 1930-7381
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- Citations: 19
Ramachandran R, Bech P, Murphy KG, et al., 2011, PLASMA GASTRIN: SOMATOSTATIN RATIO IS DECREASED IN GASTRINOMAS, Annual Meeting on British-Society-of-Gasenterology, Publisher: B M J PUBLISHING GROUP, Pages: A117-A117, ISSN: 0017-5749
Amin A, Dhillo WS, Murphy KG, 2011, The central effects of thyroid hormones on appetite., J Thyroid Res, Vol: 2011
Obesity is a major public health issue worldwide. Current pharmacological treatments are largely unsuccessful. Determining the complex pathways that regulate food intake may aid the development of new treatments. The hypothalamic-pituitary-thyroid (HPT) axis has well-known effects on energy expenditure, but its role in the regulation of food intake is less well characterised. Evidence suggests that the HPT axis can directly influence food intake. Thyroid dysfunction can have clinically significant consequences on appetite and body weight. Classically, these effects were thought to be mediated by the peripheral effects of thyroid hormone. However, more recently, local regulation of thyroid hormone in the central nervous system (CNS) is thought to play an important role in physiologically regulating appetite. This paper focuses on the role of the HPT and thyroid hormone in appetite and provides evidence for potential new targets for anti-obesity agents.
Greenwood HC, Bloom SR, Murphy KG, 2011, Peptides and their potential role in the treatment of diabetes and obesity., Rev Diabet Stud, Vol: 8, Pages: 355-368
It is estimated that 347 million people worldwide have diabetes and that over 1.5 billion adults worldwide are overweight. Predictions suggest these rates are increasing. Diabetes is a common complication in overweight and obese subjects, and in 2004, an estimated 3.4 million people died from consequences of high blood sugar. Thus, there is great interest in revealing the physiological systems that regulate body weight and blood sugar. Several peptidergic systems within the central nervous system and the periphery regulate energy homeostasis. A number of these systems have been investigated as potential treatments for obesity and the metabolic syndrome. However, manipulation of peptidergic systems poses many problems. This review discusses the peptidergic systems currently attracting research interest for their clinical potential to treat obesity. We consider first neuropeptides in the brain, including the orexigenic neuropeptide Y and melanin-concentrating hormone, and anorectic factors such as the melanocortins, ciliary neurotrophic factor, and neuromedin U. We subsequently discuss the utility of targeting peripheral gut peptides, including pancreatic polypeptide, peptide YY, amylin, and the gastric hormone ghrelin. Also, we analyze the evidence that these factors or drugs based on them may be therapeutically useful, while considering the disadvantages of using such peptides in a clinical context.
Kinsey-Jones JS, Murphy KG, 2011, Current models and strategies in the development of antiobesity drugs, ANIMAL MODELS: THEIR VALUE IN PREDICTING DRUG EFFICACY AND TOXICITY, Vol: 1245, Pages: 3-6
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- Citations: 3
Ramachandran R, Bech P, Murphy KG, et al., 2011, Plasma Somatostatin: Gastrin Ratio Improves the Diagnosis of Gastrinoma, 8th Annual ENETS Conference for the Diagnosis and Treatment of Neuroendocine Tumor Disease, Publisher: KARGER, Pages: 9-9, ISSN: 0028-3835
Liu Y-L, Ford HE, Druce MR, et al., 2010, Subcutaneous oxyntomodulin analogue administration reduces body weight in lean and obese rodents, INTERNATIONAL JOURNAL OF OBESITY, Vol: 34, Pages: 1715-1725, ISSN: 0307-0565
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- Citations: 36
McGowan BMC, Minnion JS, Murphy KG, et al., 2010, Central and peripheral administration of human relaxin-2 to adult male rats inhibits food intake, DIABETES OBESITY & METABOLISM, Vol: 12, Pages: 1090-1096, ISSN: 1462-8902
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- Citations: 16
Jayasena CN, Nijher GMK, Abbara A, et al., 2010, Twice-Weekly Administration of Kisspeptin-54 for 8 Weeks Stimulates Release of Reproductive Hormones in Women With Hypothalamic Amenorrhea, CLINICAL PHARMACOLOGY & THERAPEUTICS, Vol: 88, Pages: 840-847, ISSN: 0009-9236
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- Citations: 82
Nijher GMK, Chaudhri OB, Ramachandran R, et al., 2010, The effects of kisspeptin-54 on blood pressure in humans and plasma kisspeptin concentrations in hypertensive diseases of pregnancy, BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Vol: 70, Pages: 674-681, ISSN: 0306-5251
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- Citations: 28
Boughton CK, Patterson M, Bewick GA, et al., 2010, Alarin stimulates food intake and gonadotrophin release in male rats, BRITISH JOURNAL OF PHARMACOLOGY, Vol: 161, Pages: 601-613, ISSN: 0007-1188
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- Citations: 36
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