Abstract
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.
Originalsprog | Engelsk |
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Tidsskrift | American Journal of Physiology: Endocrinology and Metabolism |
Vol/bind | 317 |
Udgave nummer | 6 |
Sider (fra-til) | E1081-E1093 |
ISSN | 0193-1849 |
DOI | |
Status | Udgivet - 2019 |