Felipe Casanueva

Publications (10)24.31 Total impact

• Article: [The value of 18FDG-PET for localization of ectopic Cushing's syndrome due to occult bronchial carcinoid].

  Alma Prieto-Tenreiro, José Manuel Cabezas-Agrícola, Sonia Argibay, José Manuel Cameselle-Teijeiro, Felipe Casanueva
  Endocrinología y Nutrición 06/2011; 58(9):497-9.
• Article: Oleoylethanolamide: effects on hypothalamic transmitters and gut peptides regulating food intake.

  Antonia Serrano, Francisco Javier Pavón, Sulay Tovar, Felipe Casanueva, Rosa Señarís, Carlos Diéguez, Fernando Rodríguez de Fonseca
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  ABSTRACT: Recently, it has been described the role of fatty acid ethanolamides in the control of feeding behavior. Oleoylethanolamide (OEA) is a member of this family of lipid mediators regulating feeding. OEA acts suppressing feeding behavior through, at least partially, a peripheral mechanism. However, the interaction between this acylethanolamide and other orexigenic or anorexigenic mediators is mostly not well characterized. The aim of this study was to evaluate whether anorectic actions of OEA were mediated through the modulation of central and peripheral signals involved in the regulation of feeding. Experiments were performed in male Wistar rats under free-feeding and fasting conditions. We measured hypothalamic neuropeptides and monoamines by in situ hybridization and HPLC respectively as well as plasmatic levels of relevant endocrine signals. OEA administration induced changes in hypothalamic monoaminergic activity and in the anorexigenic neuropeptide CART expressed in the paraventricular nucleus (PVN) but lacked effect on neuropeptides expression in nucleus arcuatus. In addition, OEA induced peripheral changes in gut peptides, with marked effects on PYY and Ghrelin. These results further suggest that anorexigenic properties of OEA are mediated by peripheral signals and by central alterations in neuropeptides expressed by feeding-involved hypothalamic structures receiving input from peripheral sensory systems, such as the PVN.
  Neuropharmacology 03/2011; 60(4):593-601. · 4.81 Impact Factor
• Article: Pegvisomant-induced cholestatic hepatitis with jaundice in a patient with Gilbert's syndrome.

  Ignacio Bernabeu, Jose Cameselle-Teijeiro, Felipe F Casanueva, Monica Marazuela
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  ABSTRACT: We report on a patient with active acromegaly and Gilbert's syndrome who developed severe hepatic dysfunction during pegvisomant (PEGv) monotherapy. She was partially resistant to all previous therapies, including long-acting somatostatin analogs and cabergoline. Five months after starting PEGv therapy, with an already normalized IGF1, she developed cholestatic liver dysfunction with jaundice. Liver or biliary diseases including biliary sludge, cholelithiasis or liver steatosis were excluded. A liver biopsy was in keeping with drug-induced liver injury. The discontinuation of PEGv was followed by full clinical and biochemical recovery in 6 weeks. PEGv therapy was not resumed. Apart from a minimal increase of bilirubin levels, no liver function test abnormalities were found during the 4-year follow-up period after the PEGv was discontinued. Drug-induced liver injury is the most serious systemic adverse event resulting from PEGv therapy. Since patients with mild and asymptomatic liver disease could be at a higher risk of PEGv-induced hepatotoxicity, frequent monitoring of hepatic enzymes should be required in these cases.
  European Journal of Endocrinology 04/2009; 160(5):869-72. · 3.42 Impact Factor
• Article: Obestatin stimulates Akt signalling in gastric cancer cells through beta-arrestin-mediated epidermal growth factor receptor transactivation.

  Carlos J P Alvarez, María Lodeiro, Marily Theodoropoulou, Jesús P Camiña, Felipe F Casanueva, Yolanda Pazos
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  ABSTRACT: Obestatin was identified as a gut peptide encoded by the ghrelin gene that interacts with the G protein-coupled receptor, GPR39. In this work, a sequential analysis of its transmembrane signalling pathway has been undertaken to characterize the intracellular mechanisms responsible for Akt activation. The results show that Akt activation requires the phosphorylation of T308 in the A-loop by the phosphoinositide-dependent kinase 1 (PDK1) and S473 within the HM by the mammalian target of rapamycin (mTOR) kinase complex 2 (mTORC2: Rictor, mLST8, mSin1, mTOR kinase) with participation neither of G(i)(/o)-protein nor Gbetagamma dimers. Obestatin induces the association of GPR39/beta-arrestin 1/Src signalling complex resulting in the transactivation of the epidermal growth factor receptor (EGFR) and downstream Akt signalling. Upon administration of obestatin, phosphorylation of mTOR (S2448) and p70S6K1 (T389) rise with a time course that parallels that of Akt activation. Based on the experimental data obtained, a signalling pathway involving a beta-arrestin 1 scaffolding complex and EGFR to activate Akt signalling is proposed.
  Endocrine Related Cancer 02/2009; 16(2):599-611. · 4.36 Impact Factor
• Source

  Available from: Miguel López

  Article: Role of ghrelin in reproduction.

  María C García, Miguel López, Clara V Alvarez, Felipe Casanueva, Manuel Tena-Sempere, Carlos Diéguez
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  ABSTRACT: Ghrelin, the endogenous ligand of GH secretagogue receptor type 1a, has emerged as a pleiotropic modulator of diverse biological functions, including energy homeostasis and, lately reproduction. Here, we review recent reports evaluating the reproductive effects and sites of action of ghrelin, with particular emphasis regarding its role as a molecule integrating reproductive function and energy status. Data gleaned from rodent studies clearly show that besides having direct gonadal effects, ghrelin may participate in the regulation of gonadotropin secretion and it may influence the timing of puberty. In addition, experimental data showing that ghrelin and/or its receptor are expressed in normal human ovary and testis as well as in human ovarian and testicular tumors raise the possibility that the ghrelin system may be involved in the control of cell proliferation in these tumors. We propose that ghrelin either acting as an endocrine and/or paracrine signal may play a major role in the endocrine network that integrates energy balance and reproduction.
  Reproduction (Cambridge, England) 04/2007; 133(3):531-40. · 3.09 Impact Factor
• Chapter: Growth Hormone Releasing Activity of Ghrelin

  Carlos Diéguez, Fernando Cordido, Vera Popovic, Felipe Casanueva
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  ABSTRACT: The isolation of ghrelin is one of the most important breakthroughs in the understanding of the regulatory mechanisms involved in the neuroregulation of growth hormone (GH) secretion for several reasons. It gives definitive proof of the existence of a GH Secretagogue (GHS)/GHS-receptor signaling system in the control of GH secretion. Although for many years it was dogma that GH secretion by the anterior pituitary gland was the net result of the antagonistic actions of growth hormone releasing hormone (GHRH) and somatostatin, now a new physiological model of the regulation of GH secretion involving GHRH, somatostatin and ghrelin must be developed. It opens up the possibility of gaining a greater insight into the physiopathological mechanisms involved in the alterations of somatotroph cell function and somatic growth. Finally, it will allow the development of new agonist and antagonist compounds that may well be useful in the treatment of different disease states.
  04/2006: pages 61-72;
• Article: Growth hormone response to GHRH + GHRP-6 in type 2 diabetes during euglycemic and hyperglycemic clamp.

  Dragan Micic, Aleksandra Kendereski, Mirjana Sumarac-Dumanovic, Goran Cvijovic, Vera Popovic, Carlos Dieguez, Felipe Casanueva
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  ABSTRACT: The aim of this study was to investigate the effect of two different glucose levels on GH response to the combined administration of GHRH+GHRP-6 in patients with type 2 diabetes. GH response to i.v. bolus of GHRH+GHRP-6 (100 mcg, each) was measured in 12 male patients with type 2 diabetes (mean age: 53.9+/-1.59 years; BMI: 25.58+/-0.39 kg/m(2); mean HbA(1c): 8.7+/-0.42%), during a euglycemic (mean glucose: 4.92+/-0.08 mmol) hyperinsulinemic clamp (insulin infusion rate of 100 mU/kg/h) and a hyperglycemic clamp (mean glucose: 12.19+/-0.11 mmol/l). There was no difference in basal GH levels between the hyperglycemic and euglycemic clamps (2.9+/-0.99 mU/l versus 1.48+/-0.44 mU/l; P>0.05). Peak GH response to GHRH+GHRP-6 during the hyperglycemic clamp was lower than in the englycemic clamp (112.45+/-14.45 mU/l versus 151.06+/-16.87 mU/l; P<0.05). Area under the GH curve was lower in the hyperglycemic than in the euglycemic clamp (6974.49+/-1001.95 mU/l/min versus 9560.75+/-1140.65 mU/l/min; P<0.05). It is concluded that hyperglycemia significantly reduces GH response to combined administration of GHRH+GHRP-6 in normal weight patients with type 2 diabetes. It is suggested that ambient glucose levels should be taken into account during interpretation of GH response to combined administration of GHRH+GHRP-6 in patients with type 2 diabetes.
  Diabetes Research and Clinical Practice 02/2004; 63(1):37-45. · 2.75 Impact Factor
• Source

  Available from: Carlos Dieguez

  Article: Dopaminergic tone and obesity: an insight from prolactinomas treated with bromocriptine.

  Mirjana Doknic, Sandra Pekic, Milos Zarkovic, Milica Medic-Stojanoska, Carlos Dieguez, Felipe Casanueva, Vera Popovic
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  ABSTRACT: It has recently been shown that increased body weight is associated with prolactinomas and that weight loss occurs with normalization of prolactin levels. On the other hand, decreased dopaminergic tone in humans is well correlated with obesity. The objective of this study was to correlate changes in prolactin levels with leptin and body mass index (BMI) in patients with prolactinomas treated with the long-acting dopamine agonist bromocriptine (BC). Eleven female and twelve male patients, aged 36.7+/-2.6 years with BMI in males of 30.4+/-1.7 kg/m(2) and in females of 24.4+/-1.2 kg/m(2), were evaluated after 1 and 6 months and 11 patients were further evaluated after 2 years of BC therapy. Plasma prolactin is presented as the mean of four samples taken daily. Serum leptin was determined in the pooled serum from three samples taken at 15-min intervals at 0800 h after an overnight fast. Multivariate linear regression and repeated measures analysis of covariance were used. In males, pretreatment prolactin levels were 71 362+/-29 912 mU/l while leptin levels were 14.9+/-1.8 microg/l. In females, pretreatment prolactin levels were 11 395+/-5839 mU/l and leptin levels were 16.7+/-2.5 microg/l. The sexual dimorphism of serum leptin levels at initial presentation was preserved after adjusting for BMI and prolactin-induced hypogonadism. After 1 month of therapy, prolactin levels significantly decreased (males: 17 618+/-8736 mU/l, females: 3686+/-2231; P<0.05), BMI did not change (males: 30.2+/-1.7 kg/m(2), females: 24.1+/-1.2 kg/m(2); P>0.05), while serum leptin levels decreased (males: 12.5+/-1.5 microg/l, females: 13.6+/-2.1 microg/l; P<0.05). After 6 months of treatment, prolactin further decreased (males: 3456+/-2101 mU/l, females: 677+/-360 mU/l; P<0.05) as did BMI (males: 28.6+/-1.6 kg/m(2), females 23.1+/-1.0 kg/m(2); P<0.05). The difference was more pronounced in male patients. Leptin levels were 12.8+/-2.8 microg/l in males and 12.9+/-1.8 microg/l in females (P<0.05). After 2 years of BC treatment, prolactin levels were near normal (males: 665+/-439 mU/l, females 447+/-130 mU/l; P<0.05) and BMI remained 26.5+/-1.9 kg/m(2) for males and 23.6+/-0.8 kg/m(2) for females (P<0.05). Leptin levels were 9.5+/-2.2 microg/l in males and 18.7+/-3.1 microg/l in females (P<0.05). There was a gradual increase in the gender difference in serum leptin levels over time. Changes in serum leptin levels significantly correlated with changes in BMI (r=0.844, P<0.001) but did not correlate with changes in plasma prolactin levels after 1 month (r=0.166), 6 months (r=0.313) and 2 years (r=0.234, P>0.05). The long-acting dopamine agonist BC, by increasing dopaminergic tone, may influence body weight and likely body composition by mechanisms in addition to reducing hyperprolactinemia in patients with prolactinomas.
  European Journal of Endocrinology 08/2002; 147(1):77-84. · 3.42 Impact Factor
• Article: Ghrelin and the enteroinsular axis in healthy men.

  Dragan Micic, Leonidas Duntas, Goran Cvijovic, Aleksandra Kendereski, Mirjana Sumarac-Dumanovic, Peter Jehle, Svetlana Zoric, Danica Pejkovic, Mary Lague, Carlos Dieguez, Felipe Casanueva
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  ABSTRACT: Ghrelin, a potent stimulator of GH secretion, also acts as an orexigenic hormone. Plasma ghrelin levels rise before meals with postprandial reduction, suggesting that circulating levels of enteroinsular hormones might influence ghrelin secretion. The aim of this study was to evaluate the effects of ghrelin on enteroinsular hormones in healthy men. Three tests were performed on 3 different days in 6 healthy men: On the first day, saline was infused from 0-120 minutes followed by a ghrelin bolus (1 microg/kg) administration (Test 1); on the second experimental day, GHRH was administered at 0 min, and a ghrelin bolus was given at 120 min (Test 2); on the third experimental day, GHRP-6 was administered at 0 min, followed by a ghrelin bolus at 120 min (Test 3). Plasma glucose, insulin, proinsulin, C-Peptide Glucagone Like Peptide one (GLP-1) determined at 0, 15, 30, 60, 90, and 120 min of the test period. There was a significant increase in AUC glucose (526.41+/-22.91 mmol . ml(-1) . min vs. 566.37+/-15.64 mmol . ml(-1) . min; p<0.05) and AUC insulin (756.25+/-107.56 mU . ml(-1) . min vs. 981.62+/-180.32 mU . ml(-1) . min; p<0.05) and a significant decrease in AUC GLP-1 (2346.87+/-874.28 pmol . ml(-1) . min vs. 1769.5+/-784 pmol . ml(-1) . min; p<0.05) after ghrelin administration in Test 1 compared to Test 3. There was a mild but non-significant increase in AUC for insulin, proinsulin, and C-Peptide and a mild reduction in AUC GLP-1 after every ghrelin administration. There was no evidence of a direct effect of ghrelin administration on enteroinsular hormone levels in this study. However, ghrelin may potentiate the glucose-insulin stimulatory effects of GHRP-6. More studies should be carried out for further evaluation of ghrelin-enteroinsular hormones interplay.
  Hormones (Athens, Greece) 6(4):321-6. · 2.44 Impact Factor
• Article: Expression of Growth Hormone Secretagogue Receptor Type 1a, the Functional Ghrelin Receptor, in Human Ovarian Surface Epithelium Mullerian Duct Derivates and Ovarian Tumors

  Enrique Aguilar, M. Barreiro, Felipe Casanueva, Lisa Chopin, Carlos Dieguez, Felice Gaytan, Adrian Herington, Penelope Jeffery, Concepcion Morales, Manuel Tena-Sempere