1 |
Recherche de sécrétagogues naturels du GLP-1 : exploration du potentiel antidiabétique d'espèces du genre Cynanchum (Apocynaceae) / Research for natural GLP-1 secretagogues : exploration of the antidiabetic potential of Cynanchum species (Apocyanceae)Tsoukalas, Michail 14 September 2015 (has links)
Dans le cadre de la recherche de composés pouvant stimuler la sécrétion de l’hormone hypoglycémiante GLP-1 (glucagon-like-peptide 1) et sur des critères ethno-pharmacologiques et taxonomiques, différentes Asclepiadoidées ont été criblées sur un modèle cellulaire (lignée STC-1). Cette approche nous a permis de sélectionner deux espèces de Cynanchum malgaches. L’isolement bio-guidé de C. marnierianum a conduit à la purification de 2 nouveaux glycosides prégnaniques, les marnieranosides. L’exploration phytochimique de C. menarandrense a permis l’identification de 5 nouvelles structures prégnaniques et de 2 prégnanes déjà signalés dans un genre taxonomiquement proche et hypoglycémiant : Caralluma. Les prégnanes purifiés ont aussi été évalués pour leur effet sécrétagogue GLP-1 et cytotoxique mais seuls les marnieranosides se sont avérés bioactifs. Des analogies structurales entre les molécules identifiées dans le genre Cynanchum et des molécules bioactives isolées au préalable d’espèces antidiabétiques (genres Hoodia et Caralluma) valident notre stratégie pour la découverte des métabolites secondaires avec un potentiel antidiabétique. / In the framework of our search for antidiabetic compounds capable of stimulating the secretion of the hypoglycemic hormone GLP-1 (glucagon-like-peptide 1), based on ethnopharmacological and taxomic criteria, several Asclepiadoidae plants were screened with an in vitro model (STC-1 cell line). This approach led to the selection of two Malagasy Cynanchum species.Bio-guided fractionation of C. marnierianum led to the purification of two new pregnane glycosides named marnieranosides. The phytochemical study of C. menarandrense led to the identification of 5 new pregnane structures along with 2 pregnanes previously reported in the closely related and hypoglycemic Caralluma genus. The isolated pregnanes were evaluated for their GLP-1 secretagogue and cytotoxic activity but only the marnieranosides were proven bioactive. Structural similarities of the Cynanchum pregnanes with the ones previously isolated from antidiabetic plants (Hoodia and Caralluma), validated our approach for the discovery of secondary metabolites with antidiabetic potential.
|
2 |
Diabetes-Induced Expression and Regulation of GLP-1 levels by Bile Acid Receptors (TGR5 & FXR)Spengler, Joseph R 01 January 2017 (has links)
Diabetes Mellitus has continued to drastically affect the health of the world and many complications can prove fatal. As long as this metabolic disease persist, research discoveries will need to continue to be made so that patient outcomes and healthcare are dramatically enhanced. In recent years, GLP-1 has been the topic of conversation for diabetes research, due to its promising effects in promoting insulin sensitivity. Furthermore, bile acids and their receptors (TGR5 & FXR) have shown promise in their actions in the regulation of GLP-1, and thus glucose homeostasis. Here we have shown the detection and increased expression of TGR5 and GLP-1, and decreased expression of FXR in diabetic mouse intestinal mucosa tissues. We have also shown the detection and increased expression of these receptors in STC-1 cells. More importantly we have linked the connection of increased glucose concentration (hyperglycemia) to increased TGR5 activation to increased GLP-1 release, thus leading to increased insulin sensitivity and altered diabetic outcomes.
|
Page generated in 0.0146 seconds