Generation of L Cells in Mouse and Human Small Intestine Organoids

  1. Eelco J.P. de Koning1,3,4
  1. 1Hubrecht Institute/KNAW and University Medical Centre Utrecht, Utrecht, the Netherlands
  2. 2Cambridge Institute for Medical Research, Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge, U.K.
  3. 3Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands
  4. 4Department of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands
  1. Corresponding author: Natalia Petersen, n.petersen{at}hubrecht.eu, or Eelco J.P. de Koning, e.koning{at}hubrecht.eu.

Abstract

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.

Footnotes

  • Received June 27, 2013.
  • Accepted October 7, 2013.

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  1. Diabetes vol. 63 no. 2 410-420
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