Exendins are peptide hormones isolated from an exocrine gland but have endocrine actions. Exendins stimulate insulin secretion in response to rising blood glucose levels, and modulate gastric emptying to slow the entry of ingested sugars into the bloodstream. Exendin-3 is a 39-amino acid peptide that shares homology with VIP (vasoactive intestinal peptide), secretin, helospectin I and II and helodermin. It stimulates increases in cellular cAMP and amylase release from dispersed guinea pig pancreatic acini. Exendin-4, a 39-amino acid peptide originally isolated from the oral secretions of the lizard Heloderma suspectum, has been shown to share certain activities with glucagon-like-peptide-1 (GLP-1). It is an insulinotropic agent which improves glucose tolerance in humans and animals with diabetes. Exendin-4 increases insulin sensitivity via a PI-3-kinase-dependent mechanism. In the human fetal pancreas, the proliferation and differentiation of endocrine precursor cells into insulin-producing ß-cells can be positively regulated by exendin 4. Moreover, the peptide accelerates the functional maturation of fetal ß-cells as indicated by the stimulated insulin secretion in response to glucose.