title: Generation of L cells in mouse and human small intestine organoids.
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.
authors.affiliation: Hubrecht Institute/KNAW and University Medical Centre Utrecht, Utrecht, the Netherlands.
authors.forename: Natalia
authors.initials: N
authors.lastname: Petersen
authors.forename: Frank
authors.initials: F
authors.lastname: Reimann
authors.forename: Sina
authors.initials: S
authors.lastname: Bartfeld
authors.forename: Henner F
authors.initials: HF
authors.lastname: Farin
authors.forename: Femke C
authors.initials: FC
authors.lastname: Ringnalda
authors.forename: Robert G J
authors.initials: RG
authors.lastname: Vries
authors.forename: Stieneke
authors.initials: S
authors.lastname: van den Brink
authors.forename: Hans
authors.initials: H
authors.lastname: Clevers
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Gribble
authors.forename: Eelco J P
authors.initials: EJ
authors.lastname: de Koning
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D019858:Enteroendocrine Cells / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007421:Intestine, Small / Q000166:cytology* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009940:Organoids / Q000166:cytology*; D046509:Tissue Culture Techniques