Respuesta secretora de PYY1-36 y PYY3-36 en sujetos normales tras la ingesta de una comida mixta / PYY1-36 and PYY-36 secretory respose after a mixed meal in healthy individuals

Introducción: El péptido YY (PYY) tiene 36 aminoácidos y lo sintetizan fundamentalmente las células L del intestino. El PYY aumenta tras las comidas y alcanza su nadir tras el ayuno. Tras la ingestión se liberan dos formas: PYY1-36 yPYY3-36. Se ha demostrado que el PYY3-36 reduce la ingesta en humanos y roedores. Hay poca información sobre los valores plasmáticos de PYY, especialmente de PYY3-36, en respuesta a la ingestión y su relación con la respuesta de ghrelina. Objetivos: Estudiar la respuesta secretora de PYY1-36 y PYY3-36 en sujetos normales tras ingerir una comida mixta y su relación con la secreción de ghrelina total y acilada. Sujetos y métodos: Estudiamos a 8 sujetos sanos, 4 mujeres y 4 varones, con una mediana de edad de 53 (intervalo, 36-59) años. Tras el ayuno nocturno, recibieron en2 días diferentes y de forma aleatoria: una comida oral mixta estándar, que consistía en 400 ml de Isosource Energy (159 kcal/100 ml) o placebo por vía oral (400 ml de agua). Se obtuvieron muestras sanguíneas en los tiempos 0, 30, 45, 60 y 120 min para la determinación de PYY1-36, PYY3-36, ghrelina total y ghrelina acilada. Lasc omparaciones se realizaron mediante la prueba de Wilcoxon. Las correlaciones numéricas se analizaron mediante la prueba de correlación de Spearman. Se consideró significativo un valor de p 0,05.Resultados: Tras ingerir la comida, se produce un máximo de PYY1-36 (mediana[intervalo]) de 141,5 (81-198) pg/ml y no hay respuesta tras placebo, con un máximo de 92,5 (46-219) pg/ml (p = 0,04). Los valores del área bajo la curva (ABC) de PYY1-36tras la ingesta fueron 14.865 (8.032-19.822) pg/ml/min y tras placebo, 8.992 (4.455-21.382) pg/ml/min (p = 0,06). Tras ingerir la comida se produce un máximo de PYY3-36de 92,5 (59-135) pg/ml y no hay respuesta tras placebo, con un máximo de 46,5 (30-66) pg/ml (p = 0,02). Los valores del ABC de PYY3-36 tras la ingesta fueron 9.086(6.412-14.970) pg/ml/min y tras placebo, 4.984 (3.142-6.772) pg/ml/min (p = 0,012). El cociente nadir de ghrelina total/máximo de PYY1-36 disminuye de forma marcada trasla ingestión; los valores preprandiales son 7,44 (3,64-14,56) y los posprandiales, 3,55(1,64-7,16) (p = 0,03), mientras que no se modifica tras placebo. El cociente nadir deghrelina acilada/máximo de PYY3-36 disminuye de forma marcada tras la ingestión, ylos valores preprandiales son 2,03 (0,92-3) y los posprandiales, 0,73 (0,26-1,27) (p =0,02), mientras que no se modifican tras placebo. Conclusiones: En sujetos normales, PYY1-36 y PYY3-36 aumentan de forma paralelatras ingerir una comida mixta; simultáneamente, los valores de ghrelina total yacilada disminuyen. El cociente entre el nadir de ghrelina acilada y el máximo dePYY3-36 disminuye tras ingerir una comida mixta. Este conjunto de datos indica suposible participación en la regulación aguda del apetito tras la comida (AU)

Background: Peptide YY (PYY) is a 36 aminoacid peptide synthesized mostly by intestinalL cells. This peptide reaches its nadir during fasting and increases immediately after meals. After food intake, two molecular forms are released, PYY1-36 and PYY3-36. PYY3-36reduces food intake in both humans and rodents. There is scarce information about plasmatic concentrations of PYY, especially ofPYY3-36, after food ingestion, and their relationship to ghrelin. Objectives: To study PYY1-36 and PYY3-36secretory response after a mixed meal, and its relationship to total and acylated ghrelinsecretion in healthy subjects. Subjects and method: We studied eight healthy subjects, 4 women and 4 men, with a median age of 53 (range, 36-59) years. After an overnight fast, the subjects received either a mixed standard meal (400 ml Isosource Energy® [159 kcal/100 ml]) or placebo (400 ml of water) orally in random order on two different days. Blood samples were obtained at 0, 30, 45, 60 and 120 min for measurement of PYY1-36, PYY3-36, total ghrelin and acylated ghrelin. Comparisons were made by Wilcoxon’s test. Numerical correlations were performed using Spearman’s test. P-values 0.05 were considered significant. Results: After a mixed meal, PYY1-36 reached a peak of (median [range]) 141.5 (81-198)pg/ml. There was no response to placebo, with a peak of 92.5 (46-219) pg/ml (p = 0.04).The area under the curve (AUC) of PYY1-36levels after a mixed meal were 14,865 (8,032-19,822) pg/ml/min and after placebo were8,992 (4,455-21,382) pg/ml/min (p = 0.06).After ingestion of a mixed meal, PYY3-36reached a peak of 92.5 (59-135) pg/ml, with noresponse to placebo (46.5 [30-66] pg/ml) (p =0.02). The AUC of PYY3-36 levels after a mixed meal were 9,086 (6,412-14,970) pg/ml/min, and after placebo were 4,984 (3,142-6,772)pg/ml/min (p = 0.012). The quotient between nadir total ghrelin/peak PYY1-36 was markedly diminished after food ingestion, with preprandial values of 7.44 (3.64-14.56) and postprandial values of 3.55 (1.64-7.16) (p =0.03). The former quotient was unmodified by placebo. The quotient between nadir acylated ghrelin/peak PYY3-36 was markedly diminished after ingestion of a mixed meal, with preprandial values of 2.03 (0.92-3) and postprandial values of 0.73 (0.26-1.27) (p =0.02). This quotient was unmodified byplacebo .Conclusions: In healthy subjects, blood levels of both PYY1-36 and PYY3-36 increase after ingestion of a mixed meal. Simultaneously, total and acylated ghrelinlevels diminish. The quotient between nadiracylated ghrelin/peak PYY3-36 diminishes after a mixed meal. All these data suggest the possible contribution of these peptides to appetite regulation after ingestión (AU)

PYY(1-36) and PYY(3-36) secretory response after a mixed meal in healthy individuals.

BACKGROUND: Peptide YY (PYY) is a 36 amino acid peptide synthesized mostly by intestinal L cells. This peptide reaches its nadir during fasting and increases immediately after meals. After food intake, two molecular forms are released, PYY(1-36) and PYY(3-36). PYY(3-36) reduces food intake in both humans and rodents. There is scarce information about plasmatic concentrations of PYY, especially of PYY(3-36), after food ingestion, and their relationship to ghrelin. OBJECTIVES: To study PYY(1-36) and PYY(3-36) secretory response after a mixed meal, and its relationship to total and acylated ghrelin secretion in healthy subjects. SUBJECTS AND METHOD: We studied eight healthy subjects, 4 women and 4 men, with a median age of 53 (range, 36-59) years. After an overnight fast, the subjects received either a mixed standard meal (400ml Isosource Energy® [159kcal/100ml]) or placebo (400ml of water) orally in random order on two different days. Blood samples were obtained at 0, 30, 45, 60 and 120 min for measurement of PYY(1-36), PYY(3-36), total ghrelin and acylated ghrelin. Comparisons were made by Wilcoxon's test. Numerical correlations were performed using Spearman's test. P-values ≤ 0.05 were considered significant. RESULTS: After a mixed meal, PYY(1-36) reached a peak of (median [range]) 141.5 (81-198) pg/ml. There was no response to placebo, with a peak of 92.5 (46-219) pg/ml (p=0.04). The area under the curve (AUC) of PYY(1-36) levels after a mixed meal were 14,865 (8,032-19,822) pg/ml/min and after placebo were 8,992 (4,455-21,382) pg/ml/min (p=0.06). After ingestion of a mixed meal, PYY(3-36) reached a peak of 92.5 (59-135) pg/ml, with no response to placebo (46.5 [30-66] pg/ml) (p = 0.02). The AUC of PYY(3-36) levels after a mixed meal were 9,086 (6,412-14,970) pg/ml/min, and after placebo were 4,984 (3,142-6,772) pg/ml/min (p=0.012). The quotient between nadir total ghrelin/peak PYY(1-36) was markedly diminished after food ingestion, with preprandial values of 7.44 (3.64-14.56) and postprandial values of 3.55 (1.64-7.16) (p=0.03). The former quotient was unmodified by placebo. The quotient between nadir acylated ghrelin/peak PYY(3-36) was markedly diminished after ingestion of a mixed meal, with preprandial values of 2.03 (0.92-3) and postprandial values of 0.73 (0.26-1.27) (p=0.02). This quotient was unmodified by placebo. CONCLUSIONS: In healthy subjects, blood levels of both PYY(1-36) and PYY(3-36) increase after ingestion of a mixed meal. Simultaneously, total and acylated ghrelin levels diminish. The quotient between nadir acylated ghrelin/peak PYY(3-36) diminishes after a mixed meal. All these data suggest the possible contribution of these peptides to appetite regulation after ingestion.

Síndrome de Cushing por receptores corticosuprarrenales aberrantes / Cushing’s syndrome caused by aberrant adrenal receptors

En investigaciones recientes se ha demostrado que la producción de cortisol en algunos casos de síndrome de Cushing no dependiente de la corticotropina (previamente descritos como "autónomos") está regulada por la existencia de receptores de membrana aberrantes que producen un estímulo crónico de las células corticosuprarrenales, no regulado de forma negativa por glucocorticoides, y que conduce a un incremento crónico de la esteroidogénesis y (posiblemente) a la proliferación celular en la glándula. Se han descrito receptores de este tipo en casos de síndrome de Cushing para varias hormonas, entre ellas el péptido inhibidor gástrico (GIP), la arginina vasopresina (AVP), las catecolaminas, la lutropina/gonadotropina coriónica humana, la serotonina y otras. Los mecanismos moleculares que conducen a la aparición de este tipo de receptores en la corteza suprarrenal todavía son desconocidos. Esta nueva variante etiológica del síndrome de Cushing no dependiente de la corticotropina dará lugar (como así está ocurriendo) a la utilización de tratamientos farmacológicos alternativos a la adrenalectomía. Son probables la identificación futura de nuevos receptores aberrantes capaces de inducir la esteroidogénesis que causa el síndrome de Cushing y la descripción de receptores aberrantes en otros órganos endocrinos y no endocrinos (AU)

Recent studies have shown that cortisol production in some cases of adrenocorticotropic hormone (ACTH)-independent Cushing's syndrome (previously suspected as being "autonomous") is actually regulated by aberrant membrane receptors. These receptors produce a chronic stimulus on adrenal cells unregulated by the usual glucocorticoid negative feedback, thus increasing chronic steroidogenesis and possibly stimulating cellular hyperplasia. Receptors of this type have been described in cases of Cushing's syndrome caused by a several hormones: gastric inhibitor peptide (GIP), arginine-vasopressin (AVP), catecholamines, LH/hCG, serotonin (5-HT) and others. The molecular mechanisms leading to expression of this type of receptors in the adrenal cortex are still unknown. This new etiological variant of ACTH-independent Cushing's syndrome will lead (as is already happening) to the use of new pharmacological alternatives to adrenalectomy. Potentially, further studies will identify other aberrant receptors that induce steroidogenesis leading to Cushing's syndrome, as well as the presence of aberrant receptors in other endocrine and non-endocrine organs (AU)