GLP1- and GIP-producing cells rarely overlap and differ by bombesin receptor-2 expression and responsiveness

TY - JOUR

T1 - GLP1- and GIP-producing cells rarely overlap and differ by bombesin receptor-2 expression and responsiveness

AU - Svendsen, Berit

AU - Pais, Ramona

AU - Engelstoft, Maja S

AU - Milev, Nikolay B

AU - Richards, Paul

AU - Christiansen, Charlotte B

AU - Egerod, Kristoffer L

AU - Jensen, Signe Marie

AU - Habib, Abdella M

AU - Gribble, Fiona M

AU - Schwartz, Thue W

AU - Reimann, Frank

AU - Holst, Jens J

N1 - © 2016 Society for Endocrinology.

PY - 2016

Y1 - 2016

N2 - 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'.

AB - 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'.

U2 - 10.1530/joe-15-0247

DO - 10.1530/joe-15-0247

M3 - Journal article

C2 - 26483393

SN - 0022-0795

VL - 228

SP - 39

EP - 48

JO - Journal of Endocrinology

JF - Journal of Endocrinology

IS - 1

ER -