Distribution and hormonal characterization of primary murine L cells throughout the gastrointestinal tract

Glucagon-like peptide-1 (GLP-1) secreted from enteroendocrine L cells is an incretin that potentiates insulin secretion and is already applied in therapies for type 2 diabetes. However, detailed examination of L cells throughout the gastrointestinal tract remains unclear, because of difficulties in purifying scattered L cells from other cells. In the present study, we identified characteristics of L cells of the upper small intestine (UI), the lower small intestine (LI) and the colon using glucagon-green fluorescent protein-expressing mice that express GFP driven by the proglucagon promoter.

The localization and density of primary L cells were evaluated by anti-green fluorescent protein antibody reactivity. GLP-1 content, messenger ribonucleic acid (mRNA) expression levels and secretion in purified L cells were measured.

The number of L cells significantly increased toward the colon. In contrast, the GLP-1 content and secretion from L cells were higher in the UI than in the LI and colon. L cells from the UI and LI expressed notably high mRNA levels of the transcription factor, islet 1. The mRNA expression levels of peptide YY in L cells were higher in the LI than in the UI and colon. The mRNA expression levels of gastric inhibitory polypeptide in L cells from the UI were significantly higher compared with those from the LI and colon.

L cells show different numbers and characteristics throughout the gut, and they express different mRNA levels of transcription factors and gastrointestinal hormones. These results contribute to the therapeutic application of promoting GLP-1 release from L cells for the treatment of type 2 diabetes.