Generation of L Cells in Mouse and Human Small Intestine Organoids
- Natalia Petersen1⇑,
- Frank Reimann2,
- Sina Bartfeld1,
- Henner F. Farin1,
- Femke C. Ringnalda1,
- Robert G.J. Vries1,
- Stieneke van den Brink1,
- Hans Clevers1,
- Fiona M. Gribble2 and
- Eelco J.P. de Koning1,3,4⇑
- 1Hubrecht Institute/KNAW and University Medical Centre Utrecht, Utrecht, the Netherlands
- 2Cambridge Institute for Medical Research, Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge, U.K.
- 3Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands
- 4Department of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands
- Corresponding author: Natalia Petersen, , or Eelco J.P. de Koning, .
Upon a nutrient challenge, L cells produce glucagon-like peptide 1 (GLP-1), a powerful stimulant of insulin release. Strategies to augment endogenous GLP-1 production include promoting L-cell differentiation and increasing L-cell number. Here we present a novel in vitro platform to generate functional L cells from three-dimensional cultures of mouse and human intestinal crypts. We show that short-chain fatty acids selectively increase the number of L cells, resulting in an elevation of GLP-1 release. This is accompanied by the upregulation of transcription factors associated with the endocrine lineage of intestinal stem cell development. Thus, our platform allows us to study and modulate the development of L cells in mouse and human crypts as a potential basis for novel therapeutic strategies in patients with type 2 diabetes.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db13-0991/-/DC1.
- Received June 27, 2013.
- Accepted October 7, 2013.
- © 2014 by the American Diabetes Association.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.