Paracrine Crosstalk between Intestinal L- and D-cells Controls Secretion of Glucagon-Like Peptide-1 in mice
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Paracrine Crosstalk between Intestinal L- and D-cells Controls Secretion of Glucagon-Like Peptide-1 in mice. / Jepsen, Sara L.; Grunddal, Kaare V.; Wewer Albrechtsen, Nicolai J; Engelstoft, Maja S; Gabe, Maria B N; Jensen, Elisa P; Ørskov, Cathrine; Poulsen, Steen S; Rosenkilde, Mette M; Pedersen, Jens; Gribble, Fiona M; Reimann, Frank; Deacon, Carolyn F; Schwartz, Thue W; Christ, Andreas D; Martin, Rainer E; Holst, Jens J.
In: American Journal of Physiology: Endocrinology and Metabolism, Vol. 317, No. 6, 2019, p. E1081-E1093.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Paracrine Crosstalk between Intestinal L- and D-cells Controls Secretion of Glucagon-Like Peptide-1 in mice
AU - Jepsen, Sara L.
AU - Grunddal, Kaare V.
AU - Wewer Albrechtsen, Nicolai J
AU - Engelstoft, Maja S
AU - Gabe, Maria B N
AU - Jensen, Elisa P
AU - Ørskov, Cathrine
AU - Poulsen, Steen S
AU - Rosenkilde, Mette M
AU - Pedersen, Jens
AU - Gribble, Fiona M
AU - Reimann, Frank
AU - Deacon, Carolyn F
AU - Schwartz, Thue W
AU - Christ, Andreas D
AU - Martin, Rainer E
AU - Holst, Jens J
PY - 2019
Y1 - 2019
N2 - DPP-4 inhibitors, used for treatment of type 2 diabetes, act by increasing the concentrations of intact GLP-1 but at the same time they inhibit secretion of GLP-1, perhaps by a negative feed-back mechanism. We hypothesized that GLP-1 secretion is feed-back regulated by somatostatin from neighbouring D-cells, and blocking this feed-back circuit results in increased GLP-1 secretion. We used a wide range of experimental techniques including gene expression analysis, immunohistochemical approaches and the perfused mouse intestine to characterise the paracrine circuit controlling GLP-1 and somatostatin. We show that 1) antagonising the SSTr2 and SSTr5 led to increased GLP-1 and somatostatin secretion in the mouse, 2) that SS exhibits strong tonic inhibition of GLP-1 secretion preferentially through SSTr5 and 3) that the secretion of somatostatin was GLP-1 receptor dependent. We conclude that SS is a tonic inhibitor of GLP-1 secretion and interventions in the somatostain-GLP-1 paracrine loop leads to increased GLP-1 secretion.
AB - DPP-4 inhibitors, used for treatment of type 2 diabetes, act by increasing the concentrations of intact GLP-1 but at the same time they inhibit secretion of GLP-1, perhaps by a negative feed-back mechanism. We hypothesized that GLP-1 secretion is feed-back regulated by somatostatin from neighbouring D-cells, and blocking this feed-back circuit results in increased GLP-1 secretion. We used a wide range of experimental techniques including gene expression analysis, immunohistochemical approaches and the perfused mouse intestine to characterise the paracrine circuit controlling GLP-1 and somatostatin. We show that 1) antagonising the SSTr2 and SSTr5 led to increased GLP-1 and somatostatin secretion in the mouse, 2) that SS exhibits strong tonic inhibition of GLP-1 secretion preferentially through SSTr5 and 3) that the secretion of somatostatin was GLP-1 receptor dependent. We conclude that SS is a tonic inhibitor of GLP-1 secretion and interventions in the somatostain-GLP-1 paracrine loop leads to increased GLP-1 secretion.
U2 - 10.1152/ajpendo.00239.2019
DO - 10.1152/ajpendo.00239.2019
M3 - Journal article
C2 - 31503512
VL - 317
SP - E1081-E1093
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
SN - 0193-1849
IS - 6
ER -
ID: 227415046