The Role of Syntaxin-1a in Glucagon-like Peptide-1 Secretion from the Adult Mouse Intestinal L-Cell

Glucagon-like Peptide-1 (GLP-1) is an incretin secreted from intestinal L-cells. Although pathways promoting GLP-1 secretion have been characterized, little is known about the mechanism of GLP-1 exocytosis. I hypothesized that Syntaxin-1a, a core SNARE protein, is essential for GLP-1 exocytosis. Immunocytochemistry demonstrated GLP-1 and Syntaxin-1a co-localization in adult mouse intestinal cell (AMIC) cultures. AMICs responded to known secretagogues (forskolin/3-isobutyl-1-1-methylxanthine, Glucose-dependent Insulinotropic Peptide and oleoylethanolamide). AMICs from Syntaxin-1afl/fl mice were infected with adenovirus (AdV)-cre-recombinase or empty-Adv. qRT-PCR, immunocytochemistry and immunoblot demonstrated knockdown of Syntaxin-1a expression in AMICs infected with AdV-cre-recombinase. Syntaxin-1a knockdown L-cells exhibited a 1.3-fold increase in basal secretion, but the response to OEA was significantly abrogated. Thus, Syntaxin-1a plays an essential role in GLP-1 secretion from the primary, adult mouse ileal L-cell. A better understanding of the molecular mechanisms mediating GLP-1 release may provide new approaches to enhancing endogenous GLP-1 levels in Type II Diabetes.M.Sc