Type 2 diabetes mellitus is a chronic disease associated with obesity and dysregulated human feeding behavior. The hormone glucagonlike peptide 1 (GLP-1), a critical regulator of body weight, food intake, and blood glucose levels, is secreted by enteroendocrine L-cells. The paucity of Lcells in primary intestinal cell cultures including organoids and monolayers has made assays of GLP-1 secretion from primary human cells challenging. In the current paper, an analytical assay pipeline consisting of an optimized human intestinal tissue construct enriched in L-cells paired with standard antibody-based GLP-1 assays was developed to screen compounds for the development of pharmaceuticals to modulate L-cell signaling. The addition of the serotonin receptor agonist Bimu 8, optimization of R-spondin and Noggin concentrations, and utilization of vasoactive intestinal peptide (VIP) increased the density of L-cells in a primary human colonic epithelial monolayer. Additionally, the incorporation of an air−liquid interface culture format increased the L-cell number so that the signal-to-noise ratio of conventional enzyme-linked immunoassays could be used to monitor GLP-1 secretion in compound screens. To demonstrate the utility of the optimized analytical method, 21 types of beverage sweeteners were screened for their ability to stimulate GLP-1 secretion. Stevioside and cyclamate were found to be the most potent inducers of GLP-1 secretion. This platform enables the quantification of GLP-1 secretion from human primary L-cells and will have broad application in understanding L-cell formation and physiology and will improve the identification of modulators of human feeding behavior.
La medicina tradicional es un recurso alternativo para el tratamiento de múltiples síntomas asociados a patologías gastrointestinales como la inflamación. Las infusiones herbales, a diferencia de los medicamentos farmacológicos, contienen múltiples compuestos químicos de diversa naturaleza, que actúan sinérgicamente para dar una respuesta antiinflamatoria. La planta Buddleja scordioides Kunth Scrophulariaceae es conocida por sus efectos antiinflamatorios, y se utiliza comúnmente para combatir síntomas relacionados a desórdenes gastrointestinales como diarrea, dolor e inflamación. Es una planta de consumo popular y fácil de adquirir, por lo que es investigada en torno a su uso en la salud intestinal. El objetivo de esta investigación fue recopilar información de los componentes fitoquímicos presentes en Buddleja scordioides, resumir la información relacionada con la absorción, digestión y transporte de los compuestos herbales a lo largo del tracto gastrointestinal, y definir su efecto antioxidante y antiinflamatorio. Se encontró que Buddleja scordioides es una especie utilizada como planta medicinal para tratar síntomas asociados con procesos de inflamación gastrointestinal. El uso etnofarmacológico de la planta B. scordioides se encuentra respaldada por investigaciones científicas que atribuyen su actividad antioxidante y antiinflamatoria al contenido fitoquímico de la planta.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.