{"id":56149,"date":"2026-03-05T13:37:43","date_gmt":"2026-03-05T21:37:43","guid":{"rendered":"https:\/\/www.salk.edu\/?post_type=disclosure&#038;p=56149"},"modified":"2026-03-06T10:50:31","modified_gmt":"2026-03-06T18:50:31","slug":"how-do-glp-1-agonists-affect-gene-expression","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/es\/news-release\/how-do-glp-1-agonists-affect-gene-expression\/","title":{"rendered":"\u00bfC\u00f3mo afectan los agonistas de GLP-1 la expresi\u00f3n g\u00e9nica?"},"content":{"rendered":"<ul>\n<li style=\"list-style: none; padding-left: -20px !important; margin-left: -20px !important;\"><strong>Lo m\u00e1s destacado<\/strong><\/li>\n<li>Los medicamentos GLP-1 han llegado a considerarse \u201cmedicamentos milagrosos\u201d, sin embargo, los mecanismos detr\u00e1s de sus muchos nuevos beneficios para la salud han permanecido poco claros.<\/li>\n<li>Investigaciones recientes del Instituto Salk revelan el mecanismo detr\u00e1s de uno de estos beneficios: promover la salud y la tolerancia al estr\u00e9s de las c\u00e9lulas beta pancre\u00e1ticas, a largo plazo.<\/li>\n<li>Los hallazgos demuestran c\u00f3mo los medicamentos GLP-1 pueden desencadenar amplias respuestas gen\u00f3micas<\/li>\n<\/ul>\n<p>LA JOLLA\u2014Los GLP-1 se est\u00e1n ganando la reputaci\u00f3n de ser \u201cmedicamentos milagrosos\u201d. Primero caracterizados por su capacidad para mejorar la liberaci\u00f3n de insulina y tratar la diabetes, luego se descubri\u00f3 que los medicamentos promov\u00edan la p\u00e9rdida de peso y mejoraban la salud cardiovascular. Adem\u00e1s de estos sorprendentes beneficios adicionales, est\u00e1 la capacidad de los medicamentos GLP-1 para mejorar la salud de las c\u00e9lulas beta del p\u00e1ncreas. Pero, \u00bfc\u00f3mo lo est\u00e1n haciendo exactamente?<\/p>\n<figure id=\"attachment_56152\"  class=\"wp-caption alignright\"><a href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/03\/2603-pr-Montminy-authors.jpg\"><img loading=\"lazy\" decoding=\"async\" width=\"458\" height=\"137\" class=\"img-responsive wp-image-56152 size-col-md-5\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/03\/2603-pr-Montminy-authors-458x137.jpg\" alt=\"Sam Van de Velde, PhD, (left), Marc Montminy, PhD, (center), and Reuben Shaw, PhD (right) discovered that GLP-1s interact with the multi-protein complex called Mediator to cause a broad genomic response.\" srcset=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/03\/2603-pr-Montminy-authors-458x137.jpg 458w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/03\/2603-pr-Montminy-authors-300x90.jpg 300w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/03\/2603-pr-Montminy-authors-1024x307.jpg 1024w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/03\/2603-pr-Montminy-authors-768x231.jpg 768w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/03\/2603-pr-Montminy-authors-147x44.jpg 147w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/03\/2603-pr-Montminy-authors-585x176.jpg 585w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/03\/2603-pr-Montminy-authors-553x166.jpg 553w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/03\/2603-pr-Montminy-authors-750x225.jpg 750w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/03\/2603-pr-Montminy-authors-767x230.jpg 767w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/03\/2603-pr-Montminy-authors-945x284.jpg 945w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/03\/2603-pr-Montminy-authors.jpg 1166w\" sizes=\"auto, (max-width: 458px) 100vw, 458px\" \/><\/a><figcaption class=\"wp-caption-text\">Sam Van de Velde, PhD, (izquierda), Marc Montminy, PhD, (centro) y Reuben Shaw, PhD (derecha) descubrieron que los GLP-1 interact\u00faan con el complejo multiproteico llamado Mediador para provocar una respuesta gen\u00f3mica amplia.<br \/><a href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/03\/2603-pr-Montminy-authors.jpg\" target=\"_blank\" rel=\"noopener\">Haga clic aqu\u00ed<\/a> para obtener una imagen en alta resoluci\u00f3n.<br \/>Cr\u00e9dito: Instituto Salk<\/figcaption><\/figure>\n<p>Investigadores del Instituto Salk est\u00e1n profundizando en los detalles mecanicistas de c\u00f3mo los medicamentos GLP-1 promueven la viabilidad y la resistencia al estr\u00e9s en las c\u00e9lulas beta pancre\u00e1ticas. Dado que las adaptaciones del rendimiento celular surgen de cambios en la expresi\u00f3n g\u00e9nica, el equipo examin\u00f3 prote\u00ednas reguladoras que pueden \u201cactivar\u201d programas gen\u00e9ticos ventajosos durante el uso prolongado de GLP-1. Identificaron una prote\u00edna llamada Med14, que forma parte de un complejo proteico m\u00e1s grande llamado Mediador, que estaba permitiendo los cambios dependientes de GLP-1 en la expresi\u00f3n g\u00e9nica que conducen a beneficios para la salud pancre\u00e1tica.<\/p>\n<p>El estudio se public\u00f3 en <a href=\"https:\/\/www.pnas.org\/doi\/10.1073\/pnas.2536772123\" target=\"_blank\" rel=\"noopener\"><em>Actas de la Academia Nacional de Ciencias<\/em><\/a> en <span style=\"white-space: nowrap;\">4 de marzo de 2026,<\/span> y fue financiado por subvenciones federales de investigaci\u00f3n de los Institutos Nacionales de Salud y filantrop\u00eda privada.<\/p>\n<p>\u201cLos amplios efectos beneficiosos de los medicamentos a base de GLP-1 en la diabetes, las enfermedades cardiovasculares y la obesidad han generado una ola de apasionante investigaci\u00f3n cient\u00edfica a nivel de mecanismos. Nos queda la duda de \u2018\u00bfC\u00f3mo est\u00e1n causando estos efectos los GLP-1?\u2019, pregunta el autor principal.\u201d <a href=\"https:\/\/www.salk.edu\/es\/scientist\/marc-montminy\/\" target=\"_blank\" rel=\"noopener\">Marc Montminy, MD, PhD,<\/a> un bioqu\u00edmico, fisi\u00f3logo y distinguido profesor em\u00e9rito del Salk. \u201cPudimos identificar una prote\u00edna, Med14, cuya activaci\u00f3n posterior a GLP-1 ayuda a reprogramar la expresi\u00f3n g\u00e9nica de las c\u00e9lulas beta pancre\u00e1ticas para mejorar la viabilidad de las c\u00e9lulas y su producci\u00f3n de insulina.\u2019<\/p>\n<h2 style=\"font-size: 20px; margin-top: 40px;\"><strong>\u00bfQu\u00e9 son los medicamentos GLP-1?<\/strong><\/h2>\n<p>A menudo se les llama simplemente \u201cmedicamentos GLP-1\u201d o \u201cGLP\u201d,\u201d <em>receptor del p\u00e9ptido similar al glucag\u00f3n tipo 1<\/em> <em>agonistas <\/em>funciona imitando una hormona que nuestros cuerpos producen de forma natural. La hormona, llamada p\u00e9ptido similar al glucag\u00f3n-1, ayuda a regular el az\u00facar en la sangre al promover la secreci\u00f3n de insulina. Lo hacen uni\u00e9ndose a los receptores correspondientes de GLP-1 en las c\u00e9lulas beta del p\u00e1ncreas, las cuales producen y liberan insulina en el cuerpo.<\/p>\n<p>Pero los medicamentos GLP-1 difieren de su contraparte natural en una forma significativa: a diferencia de las hormonas GLP-1 fabricadas por humanos que aparecen y desaparecen r\u00e1pidamente alrededor de las comidas, los agonistas del receptor de GLP-1 artificiales pueden permanecer mucho m\u00e1s tiempo. Los investigadores de Salk sospechan que esta presencia a m\u00e1s largo plazo puede explicar algunos de los beneficios de \u201cdroga milagrosa\u201d de los medicamentos GLP-1. Pero, \u00bfqu\u00e9 hacen exactamente los medicamentos GLP-1 a nivel molecular cuando permanecen? Y \u00bfc\u00f3mo su poder de permanencia se traduce en efectos como un menor riesgo de accidente cerebrovascular o osteoartritis mejorada?<\/p>\n<p>\u201cEl hecho de que estos f\u00e1rmacos basados en nuestras hormonas sean estables parece ser importante para los efectos a m\u00e1s largo plazo que estamos observando en las c\u00e9lulas beta pancre\u00e1ticas y otros tejidos\u201d, dice el primer autor Sam Van de Velde, PhD, cient\u00edfico del laboratorio de Montminy. \u201cPara entender c\u00f3mo estamos obteniendo estos efectos a largo plazo, necesitamos estudiar estos f\u00e1rmacos en una escala de tiempo m\u00e1s larga, y eso es exactamente lo que hicimos\u201d.\u201d<\/p>\n<h2 style=\"font-size: 20px; margin-top: 40px;\"><strong>\u00bfC\u00f3mo influyen los medicamentos GLP-1 en la salud del p\u00e1ncreas?<\/strong><\/h2>\n<p>Cuando la hormona GLP-1 se encuentra con una c\u00e9lula beta pancre\u00e1tica, la cadena resultante de se\u00f1ales, prote\u00ednas y cambios en la expresi\u00f3n g\u00e9nica que conducen a la secreci\u00f3n de insulina est\u00e1 muy bien documentada. Por otro lado, los mecanismos y cambios a mayor escala de los medicamentos de GLP-1 a largo plazo son poco comprendidos.<\/p>\n<p>As\u00ed que los investigadores se embarcaron en una expedici\u00f3n de pesca molecular en una l\u00ednea celular de beta pancre\u00e1ticas. El equipo esperaba atrapar una prote\u00edna (o prote\u00ednas) que, despu\u00e9s de la activaci\u00f3n de GLP-1, tuviera una modificaci\u00f3n qu\u00edmica particular llamada fosforilaci\u00f3n. Y eso es exactamente lo que encontraron en Med14.<\/p>\n<figure id=\"attachment_56155\"  class=\"wp-caption aligncenter\"><a href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/03\/2603-pr-Montminy-microscopy.jpg\"><img loading=\"lazy\" decoding=\"async\" width=\"1024\" height=\"466\" class=\"img-responsive wp-image-56155 size-large\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/03\/2603-pr-Montminy-microscopy-1024x466.jpg\" alt=\"Small (left) and large (right) condensates of the mediator complex inside nuclei of a pancreatic beta cell-derived cell line. Salk researchers discovered that GLP-1s interact with the multi-protein complex called Mediator to cause a broad genomic response. \" srcset=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/03\/2603-pr-Montminy-microscopy-1024x466.jpg 1024w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/03\/2603-pr-Montminy-microscopy-300x137.jpg 300w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/03\/2603-pr-Montminy-microscopy-768x350.jpg 768w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/03\/2603-pr-Montminy-microscopy-1536x700.jpg 1536w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/03\/2603-pr-Montminy-microscopy-147x67.jpg 147w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/03\/2603-pr-Montminy-microscopy-458x209.jpg 458w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/03\/2603-pr-Montminy-microscopy-585x266.jpg 585w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/03\/2603-pr-Montminy-microscopy-553x252.jpg 553w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/03\/2603-pr-Montminy-microscopy-750x342.jpg 750w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/03\/2603-pr-Montminy-microscopy-767x349.jpg 767w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/03\/2603-pr-Montminy-microscopy-945x430.jpg 945w, https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/03\/2603-pr-Montminy-microscopy.jpg 2000w\" sizes=\"auto, (max-width: 1024px) 100vw, 1024px\" \/><\/a><figcaption class=\"wp-caption-text\">Condensados peque\u00f1os (izquierda) y grandes (derecha) del complejo Mediador dentro de los n\u00facleos de una l\u00ednea celular derivada de c\u00e9lulas beta pancre\u00e1ticas. Investigadores de Salk descubrieron que los GLP-1 interact\u00faan con el complejo multiproteico llamado Mediador para provocar una amplia respuesta gen\u00f3mica.<br \/><a href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2026\/03\/2603-pr-Montminy-microscopy.jpg\" target=\"_blank\" rel=\"noopener\">Haga clic aqu\u00ed<\/a> para obtener una imagen en alta resoluci\u00f3n.<br \/>Cr\u00e9dito: Instituto Salk<\/figcaption><\/figure>\n<p>Med14 es una subunidad en un complejo multiproteico llamado Mediador, que es un regulador general bien descrito de la expresi\u00f3n g\u00e9nica en todo el genoma. Para confirmar si Med14 era un v\u00ednculo integral entre los f\u00e1rmacos GLP-1 y los cambios definitivos en la expresi\u00f3n g\u00e9nica y el comportamiento de las c\u00e9lulas beta pancre\u00e1ticas, los investigadores decidieron mutar Med14, haciendo que la prote\u00edna fuera resistente a la fosforilaci\u00f3n.<\/p>\n<p>Los patrones de expresi\u00f3n g\u00e9nica asociados con la exposici\u00f3n prolongada al f\u00e1rmaco GLP-1 desaparecieron en una l\u00ednea celular de islotes pancre\u00e1ticos mutantes para Med14 y en las c\u00e9lulas beta de un modelo murino mutante para Med14. Con Med14 funcional, los programas gen\u00e9ticos beneficiosos se activaron, potenciando las c\u00e9lulas beta pancre\u00e1ticas para que crecieran y manejaran mejor los entornos ricos en az\u00facares despu\u00e9s de las comidas.<\/p>\n<h2 style=\"font-size: 20px; margin-top: 40px;\"><strong>\u00bfDe qu\u00e9 otras maneras los medicamentos GLP-1 podr\u00edan afectar al cuerpo?<\/strong><\/h2>\n<p>Ninguno de los experimentos del equipo Salk se realiz\u00f3 en humanos, pero la relevancia persiste. Por ejemplo, se sabe que algunos de los genes regulados por la fosforilaci\u00f3n de Med14 est\u00e1n relacionados con la susceptibilidad a la diabetes tipo 2 en humanos.<\/p>\n<p>\u201cNuestros hallazgos revelan inesperadamente que la fosforilaci\u00f3n de solo una peque\u00f1a parte de la prote\u00edna Med14 juega un papel importante en la respuesta a los medicamentos GLP-1 y, en t\u00e9rminos m\u00e1s amplios, en la respuesta metab\u00f3lica a las hormonas\u201d, dice <a href=\"https:\/\/www.salk.edu\/es\/scientist\/reuben-shaw\/\" target=\"_blank\" rel=\"noopener\">Reuben Shaw, Doctor en Filosof\u00eda,<\/a> profesor y titular de la C\u00e1tedra William R. Brody en Salk, y director del Centro de C\u00e1ncer Salk Designado por el Instituto Nacional del C\u00e1ncer. \u201cAhora hay muchas preguntas nuevas que responder, desde validar nuestros hallazgos en tejidos humanos hasta ver si Med14 tiene un papel similar en otras c\u00e9lulas y \u00f3rganos\u201d.\u201d<\/p>\n<p>El equipo tiene especial curiosidad sobre los efectos de la exposici\u00f3n prolongada a GLP-1 m\u00e1s all\u00e1 de las c\u00e9lulas beta pancre\u00e1ticas. Una de las mol\u00e9culas mensajeras entre el GLP-1 y el Med14, llamada AMPc, es una mol\u00e9cula mensajera de uso com\u00fan en muchas otras situaciones que no incluyen el GLP-1. Teniendo esto en cuenta, \u00bfpodr\u00edan otros f\u00e1rmacos u hormonas activar programas gen\u00e9ticos similares al GLP-1? \u00bfY qu\u00e9 est\u00e1 sucediendo en otros tejidos metab\u00f3licamente intensos, como la grasa?<\/p>\n<p>Las preguntas siguen llegando sobre la llamada \u201cdroga milagrosa\u201d, y los cient\u00edficos de Salk est\u00e1n trabajando con entusiasmo para responderlas.<\/p>\n<h2 style=\"font-size: 20px; margin-top: 40px;\"><strong>Otros autores y financiaci\u00f3n<\/strong><\/h2>\n<p>Otros autores incluyen a Jungting Yu, K. Garrett Evensen, Edmund Pakhlevanyan y April Williams de Salk.<\/p>\n<p>El trabajo fue apoyado por los National Institutes of Health (5R01 DK083834, R35 CA220538), Breakthrough T1D (INO-2022-1125-A-N), la Paul F. Glenn Foundation for Biology of Ageing Research, la Clayton Foundation for Medical Research y el Leona M. and Harry B. Helmsley Charitable Trust.<\/p>","protected":false},"featured_media":56160,"template":"","faculty":[100],"disease-research":[173,165,123,166],"class_list":["post-56149","disclosure","type-disclosure","status-publish","has-post-thumbnail","hentry","faculty-marc-montminy","disease-research-diabetes-type-1","disease-research-diabetes-type-2","disease-research-metabolism-and-diabetes","disease-research-obesity"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>How do GLP-1 agonists affect gene expression? - Salk Institute for Biological Studies<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.salk.edu\/es\/news-release\/how-do-glp-1-agonists-affect-gene-expression\/\" \/>\n<meta property=\"og:locale\" content=\"es_MX\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"How do GLP-1 agonists affect gene expression? - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"Highlights GLP-1 drugs have come to be thought of as \u201cwonder drugs,\u201d yet the mechanisms behind their many new health benefits have remained unclear New research from the Salk Institute reveals the mechanism behind one of these benefits: promoting pancreatic beta cells\u2019 health and stress tolerance, long-term The findings show how GLP-1 drugs can trigger broad genomic responses LA JOLLA\u2014GLP-1s are building a reputation as \u201cwonder drugs.\u201d First characterized for their ability to improve insulin release and treat diabetes, the drugs were later found to promote weight loss and improve cardiovascular health. In addition to these surprising bonus benefits is the ability of GLP-1 drugs to improve pancreatic beta cell health. 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