260-OR: The L-Cell Clock Is Required for Circadian GLP-1 Secretion and Maintenance of Intestinal Homeostasis

Glucagon-like peptide-1 (GLP-1) is an incretin hormone released by the intestinal L cell in response to nutrient intake. Recent studies identified a circadian rhythm in GLP-1 secretion that is disrupted in whole-body Bmal1 KO mice. However, the extent to which the L cell clock regulates circadian GLP-1 secretion and overall diurnal metabolic and intestinal homeostasis is unknown. Gcg-creERT2/+;Bmal1flox/flox KO mice with a disrupted clock in L cells, alpha cells and some CNS cells were thus generated. M/F- and age-matched KO mice had normal body weight and 24hr food intake patterns vs. all genetic and chemical controls. Upon oral glucose gavage at the known peak and trough timepoints of GLP-1 release, KO animals lost the rhythmic GLP-1 secretory pattern in association with impaired secretion (p Disclosure S. E. Martchenko: None. A. Martchenko: None. A. Biancolin: None. P. L. Brubaker: None. Funding Canadian Institutes of Health Research (PJT-15308)