In this paper, we have used incretin receptor knock-out mice and wild-type controls to evaluate the role of islet and intestinal L- and K-cell derived GLP-1 and GIP in relation to alterations in number, morphology and function of the islets and beta-cells in animal models of beta cell insult and insulin resistance, induced by multiple low dose streptozotocin or hydrocortisone treatment. This evidence concerns the gene GCG and Insulin resistance.