GLP1- and GIP-producing cells rarely overlap and differ by bombesin receptor-2 expression and responsiveness.
The incretin hormones glucagon-like peptide-1 (GLP1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted from intestinal endocrine cells, the so-called L- and K-cells. The cells are derived from a common precursor and are highly related, and co-expression of the two hormones in so-called L/K-cells has been reported. To investigate the relationship between the GLP1- and GIP-producing cells more closely, we generated a transgenic mouse model expressing a fluorescent marker in GIP-positive cells. In combination with a mouse strain with fluorescent GLP1 cells, we were able to estimate the overlap between the two cell types. Furthermore, we used primary cultured intestinal cells and isolated perfused mouse intestine to measure the secretion of GIP and GLP1 in response to different stimuli. Overlapping GLP1 and GIP cells were rare (∼5%). KCl, glucose and forskolin+IBMX increased the secretion of both GLP1 and GIP, whereas bombesin/neuromedin C only stimulated GLP1 secretion. Expression analysis showed high expression of the bombesin 2 receptor in GLP1 positive cells, but no expression in GIP-positive cells. These data indicate both expressional and functional differences between the GLP1-producing 'L-cell' and the GIP-producing 'K-cell'.
Novo Nordisk Foundation Center for Basic Metabolic ResearchUniversity of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, DenmarkDepartment of Biomedical SciencesFaculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkWellcome Trust - MRC Institute of Metabolic ScienceUniversity of Cambridge, Cambridge, UKDepartment of Neuroscience and PharmacologyUniversity of Copenhagen, Copenhagen, Denmark Novo Nordisk Foundation Center for Basic Metabolic ResearchUniversity of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, DenmarkDepartment of Biomedical SciencesFaculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkWellcome Trust - MRC Institute of Metabolic ScienceUniversity of Cambridge, Cambridge, UKDepartment of Neuroscience and PharmacologyUniversity of Copenhagen, Copenhagen, Denmark bsvendsen@sund.ku.dk.
Berit
B
Svendsen
Novo Nordisk Foundation Center for Basic Metabolic ResearchUniversity of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, DenmarkDepartment of Biomedical SciencesFaculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkWellcome Trust - MRC Institute of Metabolic ScienceUniversity of Cambridge, Cambridge, UKDepartment of Neuroscience and PharmacologyUniversity of Copenhagen, Copenhagen, Denmark.
Ramona
R
Pais
Novo Nordisk Foundation Center for Basic Metabolic ResearchUniversity of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, DenmarkDepartment of Biomedical SciencesFaculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkWellcome Trust - MRC Institute of Metabolic ScienceUniversity of Cambridge, Cambridge, UKDepartment of Neuroscience and PharmacologyUniversity of Copenhagen, Copenhagen, Denmark Novo Nordisk Foundation Center for Basic Metabolic ResearchUniversity of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, DenmarkDepartment of Biomedical SciencesFaculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkWellcome Trust - MRC Institute of Metabolic ScienceUniversity of Cambridge, Cambridge, UKDepartment of Neuroscience and PharmacologyUniversity of Copenhagen, Copenhagen, Denmark.
Maja S
MS
Engelstoft
Novo Nordisk Foundation Center for Basic Metabolic ResearchUniversity of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, DenmarkDepartment of Biomedical SciencesFaculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkWellcome Trust - MRC Institute of Metabolic ScienceUniversity of Cambridge, Cambridge, UKDepartment of Neuroscience and PharmacologyUniversity of Copenhagen, Copenhagen, Denmark.
Nikolay B
NB
Milev
Novo Nordisk Foundation Center for Basic Metabolic ResearchUniversity of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, DenmarkDepartment of Biomedical SciencesFaculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkWellcome Trust - MRC Institute of Metabolic ScienceUniversity of Cambridge, Cambridge, UKDepartment of Neuroscience and PharmacologyUniversity of Copenhagen, Copenhagen, Denmark.
Paul
P
Richards
Novo Nordisk Foundation Center for Basic Metabolic ResearchUniversity of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, DenmarkDepartment of Biomedical SciencesFaculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkWellcome Trust - MRC Institute of Metabolic ScienceUniversity of Cambridge, Cambridge, UKDepartment of Neuroscience and PharmacologyUniversity of Copenhagen, Copenhagen, Denmark Novo Nordisk Foundation Center for Basic Metabolic ResearchUniversity of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, DenmarkDepartment of Biomedical SciencesFaculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkWellcome Trust - MRC Institute of Metabolic ScienceUniversity of Cambridge, Cambridge, UKDepartment of Neuroscience and PharmacologyUniversity of Copenhagen, Copenhagen, Denmark.
Charlotte B
CB
Christiansen
Novo Nordisk Foundation Center for Basic Metabolic ResearchUniversity of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, DenmarkDepartment of Biomedical SciencesFaculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkWellcome Trust - MRC Institute of Metabolic ScienceUniversity of Cambridge, Cambridge, UKDepartment of Neuroscience and PharmacologyUniversity of Copenhagen, Copenhagen, Denmark Novo Nordisk Foundation Center for Basic Metabolic ResearchUniversity of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, DenmarkDepartment of Biomedical SciencesFaculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkWellcome Trust - MRC Institute of Metabolic ScienceUniversity of Cambridge, Cambridge, UKDepartment of Neuroscience and PharmacologyUniversity of Copenhagen, Copenhagen, Denmark.
Kristoffer L
KL
Egerod
Novo Nordisk Foundation Center for Basic Metabolic ResearchUniversity of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, DenmarkDepartment of Biomedical SciencesFaculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkWellcome Trust - MRC Institute of Metabolic ScienceUniversity of Cambridge, Cambridge, UKDepartment of Neuroscience and PharmacologyUniversity of Copenhagen, Copenhagen, Denmark Novo Nordisk Foundation Center for Basic Metabolic ResearchUniversity of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, DenmarkDepartment of Biomedical SciencesFaculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkWellcome Trust - MRC Institute of Metabolic ScienceUniversity of Cambridge, Cambridge, UKDepartment of Neuroscience and PharmacologyUniversity of Copenhagen, Copenhagen, Denmark.
Signe M
SM
Jensen
Novo Nordisk Foundation Center for Basic Metabolic ResearchUniversity of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, DenmarkDepartment of Biomedical SciencesFaculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkWellcome Trust - MRC Institute of Metabolic ScienceUniversity of Cambridge, Cambridge, UKDepartment of Neuroscience and PharmacologyUniversity of Copenhagen, Copenhagen, Denmark.
Abdella M
AM
Habib
Novo Nordisk Foundation Center for Basic Metabolic ResearchUniversity of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, DenmarkDepartment of Biomedical SciencesFaculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkWellcome Trust - MRC Institute of Metabolic ScienceUniversity of Cambridge, Cambridge, UKDepartment of Neuroscience and PharmacologyUniversity of Copenhagen, Copenhagen, Denmark.
Fiona M
FM
Gribble
Novo Nordisk Foundation Center for Basic Metabolic ResearchUniversity of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, DenmarkDepartment of Biomedical SciencesFaculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkWellcome Trust - MRC Institute of Metabolic ScienceUniversity of Cambridge, Cambridge, UKDepartment of Neuroscience and PharmacologyUniversity of Copenhagen, Copenhagen, Denmark Novo Nordisk Foundation Center for Basic Metabolic ResearchUniversity of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, DenmarkDepartment of Biomedical SciencesFaculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkWellcome Trust - MRC Institute of Metabolic ScienceUniversity of Cambridge, Cambridge, UKDepartment of Neuroscience and PharmacologyUniversity of Copenhagen, Copenhagen, Denmark.
Thue W
TW
Schwartz
Novo Nordisk Foundation Center for Basic Metabolic ResearchUniversity of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, DenmarkDepartment of Biomedical SciencesFaculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkWellcome Trust - MRC Institute of Metabolic ScienceUniversity of Cambridge, Cambridge, UKDepartment of Neuroscience and PharmacologyUniversity of Copenhagen, Copenhagen, Denmark.
Frank
F
Reimann
Novo Nordisk Foundation Center for Basic Metabolic ResearchUniversity of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, DenmarkDepartment of Biomedical SciencesFaculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkWellcome Trust - MRC Institute of Metabolic ScienceUniversity of Cambridge, Cambridge, UKDepartment of Neuroscience and PharmacologyUniversity of Copenhagen, Copenhagen, Denmark Novo Nordisk Foundation Center for Basic Metabolic ResearchUniversity of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, DenmarkDepartment of Biomedical SciencesFaculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkWellcome Trust - MRC Institute of Metabolic ScienceUniversity of Cambridge, Cambridge, UKDepartment of Neuroscience and PharmacologyUniversity of Copenhagen, Copenhagen, Denmark.
Jens J
JJ
Holst
D000818:Animals; D002118:Calcium / Q000032:analysis; D002469:Cell Separation; D002478:Cells, Cultured; D019858:Enteroendocrine Cells / Q000737:chemistry / Q000145:classification* / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D005749:Gastric Inhibitory Polypeptide / Q000032:analysis / Q000096:biosynthesis* / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000032:analysis / Q000096:biosynthesis* / Q000378:metabolism; D019426:Integrases / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018004:Receptors, Bombesin / Q000032:analysis* / Q000235:genetics
D005456:Fluorescent Dyes; D018004:Receptors, Bombesin; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; C045073:Cre recombinase; D019426:Integrases; D002118:Calcium
BB2; forskolin/IBMX; incretin hormones; neuromedin C; perfused mouse intestine