The degu, Octodon degus, is a South American hystricomorph rodent that is of interest because it develops spontaneous diabetes mellitus and has been found to have islet amyloidosis. To help clarify these problems we have cloned cDNAs encoding islet amyloid polypeptide (IAPP), insulin, and glucagon precursors from this species. The predicted amino acid sequence of degu IAPP is very similar to that of nonamyloid-forming guinea pig IAPP. In contrast, degu insulin and the C-terminal region of degu glucagon are highly divergent from those of other mammals, as is also the case in the guinea pig, suggesting the existence of some form of positive evolutionary pressure on these hormones of carbohydrate metabolism in the hystricomorph rodents.