OBJECTIVES/GOALS: In this study we sought to determine the role of glucagon-like peptide-1 (GLP-1), one of the main gut hormones in regulating glucose metabolism, after protein ingestion in patients with a history of Roux-en-Y gastric bypass (GB) and sleeve gastrectomy (SG). METHODS/STUDY POPULATION: We examined the glucose and islet-cell secretory responses to 50 g protein ingestion with and without a potent GLP-1 receptor antagonist, exendin-(9-39) [Ex-9], in 10 GB-treated subjects, 9 SG-treated, and 7 non-operated controls (CN). The groups were matched for age, BMI, fat-free mass, fasting glucose and insulin, and HbA1c. The surgical groups also were matched for weight loss and time post-surgery. No subjects had diabetes. RESULTS/ANTICIPATED RESULTS: Protein ingestion resulted in an early rise in glycemia (AUCGlucose1hr) in GB and SG, whereas CN had minimal change in glucose (p<0.05). Protein ingestion enhanced C-peptide responses in all groups, but to a larger extent in GB and SG when compared to CN (p<0.05). Early glucagon response to protein ingestion (AUCGlucagon1hr) tended to be larger in GB and SG subjects when compared to CN (p=0.07). Ex-9 increased premeal and prandial glycemia in all groups (p<0.05), but increase in early glycemia (AUCGlucose1hr) was most notable in GB (p=0.1, interaction). This glycemic effect of Ex-9 was associated with a ~25% reduction in prandial C-peptide secretion in GB and SG and ~8% increase in CN (p<0.05, interaction). Early prandial glucagon responses were larger during studies with Ex-9 compared to those without (p<0.05). DISCUSSION/SIGNIFICANCE: Our findings indicate that glucose metabolism after protein ingestion is altered after GB and SG. To our knowledge, this is the first report to demonstrate that endogenous GLP-1 contributes to glucose and islet-cell secretory response to protein ingestion, and that GB and SG exaggerate GLP-1 contribution to insulin secretion after protein ingestion.