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

Research output: Contribution to journalJournal articleResearchpeer-review

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.

In: Diabetes, Vol. 69, No. 4, 04.2020, p. 614-623.

Research output: Contribution to journalJournal articleResearchpeer-review

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, vol. 69, no. 4, pp. 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., ... 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 et al. 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. In: Diabetes. 2020 ; Vol. 69, No. 4. pp. 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 = "4",
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