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

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Standard

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.

I: Diabetes, Bind 69, Nr. 4, 04.2020, s. 614-623.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Lund, ML, Sorrentino, G, Egerod, KL, Kroone, C, Mortensen, B, Knop, FK, Reimann, F, Gribble, FM, Drucker, DJ, De Koning, EJP, Schoonjans, K, Bäckhed, F, Schwartz, TW & Petersen, N 2020, 'L-cell Differentiation Is Induced by Bile Acids Through GPBAR1 and Paracrine GLP-1 and Serotonin Signaling', Diabetes, bind 69, nr. 4, s. 614-623. https://doi.org/10.2337/db19-0764

APA

Lund, M. L., Sorrentino, G., Egerod, K. L., Kroone, C., Mortensen, B., Knop, F. K., Reimann, F., Gribble, F. M., Drucker, D. J., De Koning, E. J. P., Schoonjans, K., Bäckhed, F., Schwartz, T. W., & Petersen, N. (2020). L-cell Differentiation Is Induced by Bile Acids Through GPBAR1 and Paracrine GLP-1 and Serotonin Signaling. Diabetes, 69(4), 614-623. https://doi.org/10.2337/db19-0764

Vancouver

Lund ML, Sorrentino G, Egerod KL, Kroone C, Mortensen B, Knop FK o.a. L-cell Differentiation Is Induced by Bile Acids Through GPBAR1 and Paracrine GLP-1 and Serotonin Signaling. Diabetes. 2020 apr;69(4):614-623. https://doi.org/10.2337/db19-0764

Author

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. / L-cell Differentiation Is Induced by Bile Acids Through GPBAR1 and Paracrine GLP-1 and Serotonin Signaling. I: Diabetes. 2020 ; Bind 69, Nr. 4. s. 614-623.

Bibtex

@article{afcc7177da9a44ef848e4198bad6bea2,
title = "L-cell Differentiation Is Induced by Bile Acids Through GPBAR1 and Paracrine GLP-1 and Serotonin Signaling",
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 GPBAR1 agonist, L3740, selectively increased L-cell density in mouse and human intestinal organoids and elevated GLP-1 secretory capacity. L3740 induced expression of Gcg and transcription factors Ngn3 and NeuroD1. L3740 also increased the L-cell number and GLP-1 levels and improved glucose tolerance in vivo. Further mechanistic examination revealed that the effect of L3740 on L cells required intact GLP-1 receptor and serotonin 5-hydroxytryptamine receptor 4 (5-HT4) signaling. Importantly, serotonin signaling through 5-HT4 mimicked the effects of L3740, acting downstream of GLP-1. Thus, GPBAR1 agonists and other powerful GLP-1 secretagogues facilitate L-cell differentiation through a paracrine GLP-1–dependent and serotonin-mediated mechanism.",
author = "Lund, {Mari Lilith} and Giovanni Sorrentino and Egerod, {Kristoffer Lihme} and Chantal Kroone and Brynjulf Mortensen and Knop, {Filip Krag} and Frank Reimann and Gribble, {Fiona M.} and Drucker, {Daniel J.} and {De Koning}, {Eelco J.P.} and Kristina Schoonjans and Fredrik B{\"a}ckhed and Schwartz, {Thue W.} and Natalia Petersen",
year = "2020",
month = apr,
doi = "10.2337/db19-0764",
language = "English",
volume = "69",
pages = "614--623",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association",
number = "4",

}

RIS

TY - JOUR

T1 - L-cell Differentiation Is Induced by Bile Acids Through GPBAR1 and Paracrine GLP-1 and Serotonin Signaling

AU - Lund, Mari Lilith

AU - Sorrentino, Giovanni

AU - Egerod, Kristoffer Lihme

AU - Kroone, Chantal

AU - Mortensen, Brynjulf

AU - Knop, Filip Krag

AU - Reimann, Frank

AU - Gribble, Fiona M.

AU - Drucker, Daniel J.

AU - De Koning, Eelco J.P.

AU - Schoonjans, Kristina

AU - Bäckhed, Fredrik

AU - Schwartz, Thue W.

AU - Petersen, Natalia

PY - 2020/4

Y1 - 2020/4

N2 - 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 GPBAR1 agonist, L3740, selectively increased L-cell density in mouse and human intestinal organoids and elevated GLP-1 secretory capacity. L3740 induced expression of Gcg and transcription factors Ngn3 and NeuroD1. L3740 also increased the L-cell number and GLP-1 levels and improved glucose tolerance in vivo. Further mechanistic examination revealed that the effect of L3740 on L cells required intact GLP-1 receptor and serotonin 5-hydroxytryptamine receptor 4 (5-HT4) signaling. Importantly, serotonin signaling through 5-HT4 mimicked the effects of L3740, acting downstream of GLP-1. Thus, GPBAR1 agonists and other powerful GLP-1 secretagogues facilitate L-cell differentiation through a paracrine GLP-1–dependent and serotonin-mediated mechanism.

AB - 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 GPBAR1 agonist, L3740, selectively increased L-cell density in mouse and human intestinal organoids and elevated GLP-1 secretory capacity. L3740 induced expression of Gcg and transcription factors Ngn3 and NeuroD1. L3740 also increased the L-cell number and GLP-1 levels and improved glucose tolerance in vivo. Further mechanistic examination revealed that the effect of L3740 on L cells required intact GLP-1 receptor and serotonin 5-hydroxytryptamine receptor 4 (5-HT4) signaling. Importantly, serotonin signaling through 5-HT4 mimicked the effects of L3740, acting downstream of GLP-1. Thus, GPBAR1 agonists and other powerful GLP-1 secretagogues facilitate L-cell differentiation through a paracrine GLP-1–dependent and serotonin-mediated mechanism.

U2 - 10.2337/db19-0764

DO - 10.2337/db19-0764

M3 - Journal article

C2 - 32041793

AN - SCOPUS:85082147626

VL - 69

SP - 614

EP - 623

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 4

ER -

ID: 243062169