10 results on '"Dhillo WS"'
Search Results
2. Preserved C-peptide in survivors of COVID-19: Post hoc analysis.
- Author
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Clarke SA, Phylactou M, Patel B, Mills EG, Muzi B, Izzi-Engbeaya C, Khoo B, Meeran K, Comninos AN, Abbara A, Tan T, Oliver N, and Dhillo WS
- Subjects
- C-Peptide, Humans, SARS-CoV-2, Survivors, COVID-19
- Published
- 2022
- Full Text
- View/download PDF
3. The effects of kisspeptin on β-cell function, serum metabolites and appetite in humans.
- Author
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Izzi-Engbeaya C, Comninos AN, Clarke SA, Jomard A, Yang L, Jones S, Abbara A, Narayanaswamy S, Eng PC, Papadopoulou D, Prague JK, Bech P, Godsland IF, Bassett P, Sands C, Camuzeaux S, Gomez-Romero M, Pearce JTM, Lewis MR, Holmes E, Nicholson JK, Tan T, Ratnasabapathy R, Hu M, Carrat G, Piemonti L, Bugliani M, Marchetti P, Johnson PR, Hughes SJ, James Shapiro AM, Rutter GA, and Dhillo WS
- Subjects
- Adolescent, Adult, Cell Line, Glucose metabolism, Healthy Volunteers, Humans, Insulin blood, Male, Young Adult, Appetite drug effects, Insulin Secretion drug effects, Insulin-Secreting Cells drug effects, Kisspeptins pharmacology
- Abstract
Aims: To investigate the effect of kisspeptin on glucose-stimulated insulin secretion and appetite in humans., Materials and Methods: In 15 healthy men (age: 25.2 ± 1.1 years; BMI: 22.3 ± 0.5 kg m
-2 ), we compared the effects of 1 nmol kg-1 h-1 kisspeptin versus vehicle administration on glucose-stimulated insulin secretion, metabolites, gut hormones, appetite and food intake. In addition, we assessed the effect of kisspeptin on glucose-stimulated insulin secretion in vitro in human pancreatic islets and a human β-cell line (EndoC-βH1 cells)., Results: Kisspeptin administration to healthy men enhanced insulin secretion following an intravenous glucose load, and modulated serum metabolites. In keeping with this, kisspeptin increased glucose-stimulated insulin secretion from human islets and a human pancreatic cell line in vitro. In addition, kisspeptin administration did not alter gut hormones, appetite or food intake in healthy men., Conclusions: Collectively, these data demonstrate for the first time a beneficial role for kisspeptin in insulin secretion in humans in vivo. This has important implications for our understanding of the links between reproduction and metabolism in humans, as well as for the ongoing translational development of kisspeptin-based therapies for reproductive and potentially metabolic conditions., (© 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)- Published
- 2018
- Full Text
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4. Hypothalamic arcuate nucleus glucokinase regulates insulin secretion and glucose homeostasis.
- Author
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Ma Y, Ratnasabapathy R, Izzi-Engbeaya C, Nguyen-Tu MS, Richardson E, Hussain S, De Backer I, Holton C, Norton M, Carrat G, Schwappach B, Rutter GA, Dhillo WS, and Gardiner J
- Subjects
- Animals, Diabetes Mellitus, Experimental blood, Diabetes Mellitus, Type 2 blood, Glucose Tolerance Test, Homeostasis physiology, Male, Rats, Rats, Wistar, Rats, Zucker, Arcuate Nucleus of Hypothalamus enzymology, Diabetes Mellitus, Experimental enzymology, Diabetes Mellitus, Type 2 enzymology, Glucokinase metabolism, Glucose metabolism, Insulin Secretion physiology
- Abstract
Aims: To investigate the role of arcuate glucokinase (GK) in the regulation of glucose homeostasis., Materials and Methods: A recombinant adeno-associated virus expressing either GK or an antisense GK construct was used to alter GK activity specifically in the hypothalamic arcuate nucleus (arc). GK activity in this nucleus was also increased by stereotactic injection of the GK activator, compound A. The effect of altered arc GK activity on glucose homeostasis was subsequently investigated using glucose and insulin tolerance tests., Results: Increased GK activity specifically within the arc increased insulin secretion and improved glucose tolerance in rats during oral glucose tolerance tests. Decreased GK activity in this nucleus reduced insulin secretion and increased glucose levels during the same tests. Insulin sensitivity was not affected in either case. The effect of arc GK was maintained in a model of type 2 diabetes., Conclusions: These results demonstrate a role for arc GK in systemic glucose homeostasis., (© 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)
- Published
- 2018
- Full Text
- View/download PDF
5. Glucagon increases energy expenditure independently of brown adipose tissue activation in humans.
- Author
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Salem V, Izzi-Engbeaya C, Coello C, Thomas DB, Chambers ES, Comninos AN, Buckley A, Win Z, Al-Nahhas A, Rabiner EA, Gunn RN, Budge H, Symonds ME, Bloom SR, Tan TM, and Dhillo WS
- Subjects
- Adult, Cold Temperature, Controlled Before-After Studies, Fluorodeoxyglucose F18, Healthy Volunteers, Humans, Male, Positron-Emission Tomography methods, Random Allocation, Thermogenesis drug effects, Tomography, X-Ray Computed, Young Adult, Adipose Tissue, Brown metabolism, Energy Metabolism drug effects, Glucagon pharmacokinetics
- Abstract
Aims: To investigate, for a given energy expenditure (EE) rise, the differential effects of glucagon infusion and cold exposure on brown adipose tissue (BAT) activation in humans., Methods: Indirect calorimetry and supraclavicular thermography was performed in 11 healthy male volunteers before and after: cold exposure; glucagon infusion (at 23 °C); and vehicle infusion (at 23 °C). All volunteers underwent (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)/CT scanning with cold exposure. Subjects with cold-induced BAT activation on (18)F-FDG PET/CT (n = 8) underwent a randomly allocated second (18)F-FDG PET/CT scan (at 23 °C), either with glucagon infusion (n = 4) or vehicle infusion (n = 4)., Results: We observed that EE increased by 14% after cold exposure and by 15% after glucagon infusion (50 ng/kg/min; p < 0.05 vs control for both). Cold exposure produced an increase in neck temperature (+0.44 °C; p < 0.001 vs control), but glucagon infusion did not alter neck temperature. In subjects with a cold-induced increase in the metabolic activity of supraclavicular BAT on (18)F-FDG PET/CT, a significant rise in the metabolic activity of BAT after glucagon infusion was not detected. Cold exposure increased sympathetic activation, as measured by circulating norepinephrine levels, but glucagon infusion did not., Conclusions: Glucagon increases EE by a similar magnitude compared with cold activation, but independently of BAT thermogenesis. This finding is of importance for the development of safe treatments for obesity through upregulation of EE., (© 2015 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)
- Published
- 2016
- Full Text
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6. Central and peripheral administration of human relaxin-2 to adult male rats inhibits food intake.
- Author
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McGowan BM, Minnion JS, Murphy KG, White NE, Roy D, Stanley SA, Dhillo WS, Gardiner JV, Ghatei MA, and Bloom SR
- Subjects
- Animals, Eating physiology, Feeding Behavior physiology, Injections, Intraventricular, Male, Rats, Rats, Wistar, Relaxin pharmacology, Eating drug effects, Feeding Behavior drug effects, Relaxin administration & dosage
- Abstract
Aim: Relaxin is a polypeptide hormone involved in pregnancy and lactation. It is mainly secreted by the corpus luteum and placenta, but is expressed in a number of other tissues, including heart and brain. Within the brain, relaxin is expressed in the olfactory and limbic systems, the cortex and the hypothalamic arcuate nucleus (ARC). Its cognate receptor, relaxin family peptide receptor 1 (RXFP1), is also widely expressed in the brain, including the hypothalamic ARC and paraventricular nucleus (PVN), areas important in appetite regulation. The aim of this study was to investigate whether relaxin influences food intake through central hypothalamic circuits., Methods: The human form of relaxin, human relaxin-2 (H2) was administered centrally and peripherally to male Wistar rats and food intake measured. Behaviour was also assessed., Results: Intracerebroventricular (ICV) administration of H2 significantly decreased 1-h food intake in the early dark phase [2.95 ± 0.45 g (saline) vs. 0.95 ± 0.18 g (180 pmol H2), p < 0.001]. ICV administration of H2 decreased feeding behaviour and increased grooming and headdown behaviour. Intraparaventricular injections of H2 significantly decreased 1-h food intake in the early dark phase [3.13 ± 0.35 g (saline) vs. 1.35 ± 0.33 g (18 pmol H2), p < 0.01, 1.61 ± 0.31 g (180 pmol H2), p < 0.05 and 1.23 ± 0.32 g (540 pmol H2), p < 0.001]. Intraperitoneal (IP) administration of H2 significantly decreased 1-h food intake in the early dark phase [4.63 ± 0.46 g (vehicle) vs. 3.08 ± 0.15 g (66 nmol H2), p < 0.01, 3.00 ± 0.17 g (200 nmol H2), p < 0.01 and 2.26 ± 0.36 g (660 nmol H2), p < 0.001]., Conclusions: Central and peripheral administration of H2 reduces the food intake in rats. This effect may be mediated via the PVN and/or other brain regions., (© 2010 Blackwell Publishing Ltd.)
- Published
- 2010
- Full Text
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7. Cerebellin1 is a novel orexigenic peptide.
- Author
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Gardiner JV, Beale KE, Roy D, Boughton CK, Bataveljic A, Campbell DC, Bewick GA, Patel NA, Patterson M, Leavy EM, Ghatei MA, Bloom SR, and Dhillo WS
- Subjects
- Animals, Appetite Regulation physiology, Fasting, Hypothalamus physiology, Injections, Intraventricular, Male, Rats, Appetite Depressants administration & dosage, Appetite Regulation drug effects, Eating drug effects, Hypothalamus drug effects, Nerve Tissue Proteins administration & dosage, Protein Precursors administration & dosage
- Abstract
Aim: Cerebellin1 (Cbln1) is highly expressed in the hypothalamus, a region of the brain involved in appetite regulation. However, the effects of Cbn1 on food intake are not known. The present study aimed to investigate the effect of Cbln1 on appetite regulation in rats., Methods: We determined the effect of (i) intracerebroventricular (ICV) injection of Cbln1 on food intake, behaviour and plasma pituitary hormone levels in male Wistar rats; (ii) Cbln1 on the release of hypothalamic neuropeptides known to modulate food intake from hypothalamic explants and (iii) fasting on hypothalamic Cbln1 mRNA expression., Results: (i) ICV administration of Cbln1 significantly increased food intake in rats and caused no adverse behaviours. ICV administration of Cbln1 significantly reduced plasma thyroid stimulating hormone (TSH) levels 10 min postinjection in rats. (ii) Cbln1 significantly increased the release of neuropeptide Y (NPY) from hypothalamic explants. (iii) Cbln1 mRNA expression levels were increased in the ventromedial nucleus of the hypothalamus in fasted rats., Conclusions: These data suggest that Cbln1 is a novel orexigenic peptide, which may mediate its effects via hypothalamic NPY., (© 2010 Blackwell Publishing Ltd.)
- Published
- 2010
- Full Text
- View/download PDF
8. The thyroid hormone derivative 3-iodothyronamine increases food intake in rodents.
- Author
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Dhillo WS, Bewick GA, White NE, Gardiner JV, Thompson EL, Bataveljic A, Murphy KG, Roy D, Patel NA, Scutt JN, Armstrong A, Ghatei MA, and Bloom SR
- Subjects
- Animals, Arcuate Nucleus of Hypothalamus metabolism, Injections, Intraperitoneal, Male, Mice, Mice, Inbred C57BL, Motor Activity drug effects, Oxygen Consumption drug effects, Rats, Rats, Wistar, Arcuate Nucleus of Hypothalamus drug effects, Biogenic Amines administration & dosage, Brain drug effects, Eating drug effects, Thyronines administration & dosage
- Abstract
Background: The thyroid hormone derivative 3-iodothyronamine (T(1)AM), an endogenous biogenic amine, is a potent agonist of the G protein-coupled trace amine-associated receptor 1 (TAAR1). T(1)AM is present in rat brain, and TAAR1 is expressed in hypothalamic nuclei associated with the regulation of energy homeostasis., Aim: The aim of this study was to determine the effects of T(1)AM on food intake in rodents., Methods: We determined the effect of (i) intraperitoneal (i.p.) administration of T(1)AM on food intake, oxygen consumption (VO(2)) and locomotor activity in mice; (ii) intracerebroventricular (ICV) injection of T(1)AM on food intake in male rats; (iii) c-fos expression following ventricular administration of T(1)AM in male rats; and (iv) direct injection of T(1)AM into the arcuate nucleus (ARC) of male rats on food intake., Results: (i) T(1)AM (4 nmol/kg) significantly increased food intake following i.p. injection in mice but had no effect on VO(2) or locomotor activity. (ii) ICV administration of T(1)AM (1.2 nmol/kg) significantly increased food intake in male rats. (iii) Intraventricular administration of T(1)AM significantly increased c-fos expression in the ARC of male rats. (iv) Direct administration of T(1)AM (0.12, 0.4 and 1.2 nmol/kg) into the ARC of male rats significantly increased food intake., Conclusion: These data suggest that T(1)AM is an orexigenic factor that may act through the ARC to increase food intake in rodents.
- Published
- 2009
- Full Text
- View/download PDF
9. Co-administration of SR141716 with peptide YY3-36 or oxyntomodulin has additive effects on food intake in mice.
- Author
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White NE, Dhillo WS, Liu YL, Small CJ, Kennett GA, Gardiner JV, Ghatei MA, and Bloom SR
- Subjects
- Animals, Dose-Response Relationship, Drug, Drug Therapy, Combination, Eating physiology, Fasting metabolism, Fasting psychology, Mice, Obesity prevention & control, Oxyntomodulin administration & dosage, Peptide Fragments, Peptide YY administration & dosage, Piperidines administration & dosage, Pyrazoles administration & dosage, Rimonabant, Treatment Outcome, Eating drug effects, Oxyntomodulin pharmacology, Peptide YY pharmacology, Piperidines pharmacology, Pyrazoles pharmacology
- Abstract
Background: SR141716 has been shown to significantly inhibit food intake and reduce body weight by antagonizing CB(1) receptors. The gut hormones peptide YY(3-36) (PYY(3-36)) and oxyntomodulin (OXM) inhibit food intake through Y(2) and Glucagon-Like-Peptide (GLP)-1 receptors respectively., Objective: To determine the effects of co-administration of SR141716 with either PYY(3-36) or OXM in mice on food intake., Methods: Mice (n = 14 per group) were fasted for 16 h prior to study days and given two intraperitoneal injections: study 1, vehicle-saline, SR141716-saline, vehicle-PYY3-36 or SR141716-PYY3-36; study 2: vehicle-saline, SR141716-saline, vehicle-OXM or SR141716-OXM. Food was returned and measured following injections., Results: Co-administration of SR141716-PYY(3-36) or SR141716-OXM showed greater inhibition in food intake when compared with administration of SR141716, PYY(3-36) or OXM alone., Conclusion: Our data show that SR141716 in combination with PYY(3-36) or OXM reduces food intake additively in mice.
- Published
- 2008
- Full Text
- View/download PDF
10. Low-dose oral tri-iodothyronine does not directly increase food intake in man.
- Author
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Martin NM, Small CJ, Lee JL, Ellis S, Dhillo WS, Smith KL, Kong WM, Frost GS, and Bloom SR
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- Administration, Oral, Adult, Cross-Over Studies, Double-Blind Method, Eating physiology, Energy Intake physiology, Energy Metabolism physiology, Humans, Male, Thyrotropin blood, Triiodothyronine blood, Eating drug effects, Triiodothyronine administration & dosage
- Abstract
Previously, we have shown that low-dose tri-iodothyronine (T3) increases food intake in rodents. This randomised, double-blind, placebo-controlled study aimed to investigate the effects of low-dose T3 on food intake in normal body weight individuals. However, despite an elevation in fT3 comparable to our earlier studies, administration of low-dose T3 in the fasted state did not stimulate food intake in man.
- Published
- 2007
- Full Text
- View/download PDF
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