L-Cell Differentiation Is Induced by Bile Acids Through GPBAR1 and Paracrine GLP-1 and Serotonin Signaling

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L-Cell Differentiation Is Induced by Bile Acids Through GPBAR1 and Paracrine GLP-1 and Serotonin Signaling
 
Lund, Mari Lilith; Sorrentino, Giovanni; Egerod, Kristoffer Lihme; Kroone, Chantal; Mortensen, Brynjulf; Knop, Filip Krag; Reimann, Frank; Gribble, Fiona M; Drucker, Daniel J; de Koning, Eelco J P; Schoonjans, Kristina; Bäckhed, Fredrik; Schwartz, Thue W; Petersen, Natalia
(2020) Diabetes, volume 69, issue 4, pp. 614 - 623
(Article)
Abstract
Glucagon-like peptide 1 (GLP-1) mimetics are effective drugs for treatment of type 2 diabetes, and there is consequently extensive interest in increasing endogenous GLP-1 secretion and L-cell abundance. Here we identify G-protein-coupled bile acid receptor 1 (GPBAR1) as a selective regulator of intestinal L-cell differentiation. Lithocholic acid and the synthetic ... read more
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Keywords: Animals, Bile Acids and Salts/pharmacology, Cell Differentiation/drug effects, Enteroendocrine Cells/drug effects, Female, Glucagon-Like Peptide 1/metabolism, Glucagon-Like Peptide-1 Receptor/metabolism, Humans, Jejunum/drug effects, Male, Mice, Paracrine Communication/drug effects, Receptors, G-Protein-Coupled/metabolism, Serotonin/metabolism, Signal Transduction/drug effects, Internal Medicine, Endocrinology, Diabetes and Metabolism, Research Support, Non-U.S. Gov't, Journal Article
DOI: https://doi.org/10.2337/db19-0764
ISSN: 0012-1797
Publisher: American Diabetes Association Inc.
Note: Funding Information: Acknowledgments. The authors would like to thank Stine Lindberg Vedersø and Barbara Thaysen for technical assistance with the in vivo studies and Anna Sofie Husted for help with graphical design (all from the Novo Nordisk Foundation Center for Basic Metabolic Research). The authors gratefully acknowledge the support of the Core Facility for Integrated Microscopy (University of Copenhagen). Funding. G.S. is supported by a long-term Federation of European Biochemical Societies fellowship. Work in the Reimann/Gribble laboratory is supported by the Wellcome Trust (106262/Z/14/Z, 106263/Z/14/Z) and the UK Medical Research Council (MRC_MC_UU_12012/3). The Novo Nordisk Foundation Center for Basic Metabolic Research (https://www.metabol.ku.dk) is supported by an unconditional grant from the Novo Nordisk Foundation to the University of Copenhagen (NNF10CC1016515). The study was supported by the Novo Nordisk Foundation Challenge grant NNF14OC0016798 to F.B. and the University of Copenhagen Challenge grant NNF15OC0013655 to T.W.S. This work was supported by the Swiss National Science Foundation (Sinergia CRSII5_180317/1_125487) and the Ecole Polytechnique Fédérale de Lausanne (EPFL). Duality of Interest. No potential conflicts of interest relevant to this article were reported. Author Contributions. M.L.L., G.S., K.L.E., C.K., and N.P. performed the research and analyzed and interpreted the experiments. M.L.L., F.B., T.W.S., and N.P. wrote the manuscript with input from all of the other authors. M.L.L., T.W.S., and N.P. conceived the study and designed experiments. B.M., F.K.K., and F.B. provided key samples and expertise. F.R., F.M.G., D.J.D., and K.S. provided essential mouse lines for the study and edited the manuscript. E.J.P.d.K., K.S., and F.B. designed studies. N.P. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Prior Presentation. Parts of this study were presented in abstract form at the 17th Copenhagen Bioscience Conference – Intestinal Organoids, Hillerød, Denmark, 29 September–2 October 2019. Funding Information: G.S. is supported by a long-term Federation of European Biochemical Societies fellowship. Work in the Reimann/Gribble laboratory is supported by the Wellcome Trust (106262/Z/14/Z, 106263/Z/14/Z) and the UK Medical Research Council (MRC_MC_UU_12012/3). The Novo Nordisk Foundation Center for Basic Metabolic Research (https://www.metabol.ku.dk) is supported by an unconditional grant from the Novo Nordisk Foundation to the University of Copenhagen (NNF10CC1016515). The study was supported by the Novo Nordisk Foundation Challenge grant NNF14OC0016798 to F.B. and the University of Copenhagen Challenge grant NNF15OC0013655 to T.W.S. This work was supported by the Swiss National Science Foundation (Sinergia CRSII5_180317/1_125487) and the Ecole Polytechnique Fédérale de Lausanne (EPFL). Publisher Copyright: © 2020 by the American Diabetes Association.
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