• Here we show that glucagon-like peptide-1 (GLP-1) is secreted from a subpopulation of α cells within human islets. • Human islets secrete ∼50-fold more GLP-1 than murine islets and that ∼40% of the total human α cells contain GLP-1. • We observed significantly more GLP-1+ α cells in islets from donors with type 2 diabetes than in islets from donors with no diabetes. • GLP-1+ α cells can also be detected in pancreatic islet sections obtained from living donors undergoing surgery. • GLP-1 receptor signaling may support insulin secretion to a greater extent in type 2 diabetes.