Paracrine Crosstalk Between Intestinal L- and D-cells Controls Secretion of Glucagon-like Peptide-1 in Mice

Overview

Journal Am J Physiol Endocrinol Metab

Publisher American Physiological Society

Specialties Endocrinology
Physiology

Date 2019 Sep 11

PMID 31503512

Citations 23

Authors

Sara L Jepsen

Kaare V Grunddal

Nicolai J Wewer Albrechtsen

Maja S Engelstoft

Maria B N Gabe

Elisa P Jensen

Cathrine Orskov

Steen S Poulsen

Mette M Rosenkilde

Jens Pedersen

Fiona M Gribble

Frank Reimann

Carolyn F Deacon

Thue W Schwartz

Andreas D Christ

Rainer E Martin

Jens J Holst

Affiliations

Soon will be listed here.

Abstract

DPP-4 inhibitors, used for treatment of type 2 diabetes, act by increasing the concentrations of intact glucagon-like peptide-1 (GLP-1), but at the same time, they inhibit secretion of GLP-1, perhaps by a negative feedback mechanism. We hypothesized that GLP-1 secretion is feedback regulated by somatostatin (SS) from neighboring D-cells, and blocking this feedback 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 characterize the paracrine circuit controlling GLP-1 and SS. We show that ) antagonizing the SS receptor (SSTr) 2 and SSTr5 led to increased GLP-1 and SS secretion in the mouse, ) SS exhibits strong tonic inhibition of GLP-1 secretion preferentially through SSTr5, and ) the secretion of S 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 lead to increased GLP-1 secretion.

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