Generation of L cells in mouse and human small intestine organoids
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Generation of L cells in mouse and human small intestine organoids. / Petersen, Natalia; Reimann, Frank; Bartfeld, Sina; Farin, Henner F; Ringnalda, Femke C; Vries, Robert G J; van den Brink, Stieneke; Clevers, Hans; Gribble, Fiona M; de Koning, Eelco J P.
In: Diabetes, Vol. 63, No. 2, 02.2014, p. 410-20.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Generation of L cells in mouse and human small intestine organoids
AU - Petersen, Natalia
AU - Reimann, Frank
AU - Bartfeld, Sina
AU - Farin, Henner F
AU - Ringnalda, Femke C
AU - Vries, Robert G J
AU - van den Brink, Stieneke
AU - Clevers, Hans
AU - Gribble, Fiona M
AU - de Koning, Eelco J P
PY - 2014/2
Y1 - 2014/2
N2 - 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.
AB - 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.
KW - Animals
KW - Cell Culture Techniques
KW - Enteroendocrine Cells
KW - Gene Expression Regulation
KW - Humans
KW - Intestine, Small
KW - Mice
KW - Mice, Inbred C57BL
KW - Organoids
KW - Tissue Culture Techniques
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.2337/db13-0991
DO - 10.2337/db13-0991
M3 - Journal article
C2 - 24130334
VL - 63
SP - 410
EP - 420
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 2
ER -
ID: 172512839