Localization of Glucagon-Like Peptide-2 Receptor Expression in the Mouse

Abstract

Glucagon-like peptide-2 (GLP-2), secreted from enteroendocrine cells, attenuates gut motility, enhances barrier function, and augments nutrient absorption, actions mediated by a single GLP-2 receptor (GLP-2R). Despite extensive analyses, the precise distribution and cellular localization of GLP-2R expression remains controversial, confounded by the lack of suitable GLP-2R antisera. Here, we reassessed murine Glp2r expression using regular and real-time quantitative PCR (qPCR), in situ hybridization (ISH), and a Glp2rLacZ reporter mouse. Glp2r mRNA expression was detected from the stomach to the rectum and most abundant in the jejunum. Glp2r transcripts were also detected in cerebral cortex, mesenteric lymph nodes, gallbladder, urinary bladder, and mesenteric fat. Surprisingly, Glp2r mRNA was found in testis by qPCR at levels similar to jejunum. However, the testis Glp2r transcripts, detected by different primer pairs and qPCR, lacked 5′ mRNA coding sequences, and only a minute proportion of them corresponded to full-length Glp2r mRNA. Within the gut, Glp2r-driven LacZ expression was localized to enteric neurons and lamina propria stromal cells, findings confirmed by ISH analysis of the endogenous Glp2r mRNA. Unexpectedly, vascular Glp2rLacZ expression was localized to mesenteric veins and not arteries. Moreover, mesenteric fat Glp2rLacZ expression was detected within blood vessels and not adipocytes. Reporter LacZ expression was not detected in all tissues expressing an endogenous Glp2r transcript, such as gallbladder, urinary bladder, and mesenteric lymph nodes. Collectively, these findings extend our understanding of the cellular domains of Glp2r expression and highlight limitations inherent in application of commonly used technologies to infer analysis of gene expression.

GLP-2 Is Locally Produced From Human Islets and Balances Inflammation Through an Inter-Islet-Immune Cell Crosstalk

“…In line with this, GLP-2 acutely stimulates glucagon secretion (11). Consistent but low GLP-2R mRNA was confirmed in rodent acell lines as well as in a human b-cell line and in mouse islets (12), the latter being in contrast to a more recent study (13). GLP-2 had no effect on glucose-stimulated insulin secretion (GSIS) in isolated mouse islets (12).…”

Emerging Role of Lymphatics in the Regulation of Intestinal Lipid Mobilization

“…The GLP-2R is not expressed on enterocytes (El-Jamal et al, 2014;Pedersen et al, 2015) that are responsible for CM intracellular synthesis and assembly. Instead, it is mostly identified on enteric neurons, myofibroblasts, and stromal cells (Yusta et al, 2000(Yusta et al, , 2019Ørskov et al, 2005;Guan et al, 2006;Wismann et al, 2017), which are abundantly present in the subepithelial regions of the intestine, including the lamina propria. It has been suggested that GLP-2-induced intestinal wound repair may involve vascular endothelial growth factor (VEGF) secretion from fibroblasts (Bulut et al, 2008).…”

Teduglutide Therapy in 2 Patients With Short‐Bowel Syndrome and Familial Adenomatous Polyposis

“…1 Nonetheless, improved techniques suggest GLP-2R localization in subsets of subepithelial myofibroblasts, enteric neurons, and enteroendocrine cells from stomach to rectum. 5,6 Indeed, its expression in subepithelial myofibroblasts may represent the recently identified telocytes, which communicate with enteric neurons and the intestinal epithelium to mediate enterocyte proliferation, differentiation, migration, and repair in a paracrine manner. 7 In addition to GLP-2R expression, the proliferative effects of GLP-2 have been noted from duodenum to colon [8][9][10][11] ; therefore, its ability to amplify upper or lower gastrointestinal polyposis in patients with FAP cannot be excluded.…”