GLP-2 is related in sequence to GLP-1, glucagon, GIP and other members of the glucagon peptide superfamily. Many of these peptides exhibit an alanine at position 2, rendering them ideal substrates for degradation by the enzyme DP IV. Indeed, Analysis of circulating forms of GLP-2 in rodents and humans confirms that both GLP-21-33 and GLP-23-33 are detected in the fasting and postprandial states. Consistent with the importance of DP IV for GLP-2 bioactivity and degradation, a relatively larger amount of GLP-2 is required to stimulate GLP-2-dependent endpoints in rats compared to mice, as the former exhibit comparatively greater levels of circulating DP IV activity. Accordingly, analogues of GLP-2 that are resistant to DP IV-mediated degradation are more potent than the native peptide in vivo.