As noted by Ling et al, impairment of GLP-1R signalling did not affect pancreatic insulin or glucagon but increased the number of islets with centralised alpha cells. Abolition of incretin signalling also decreased the number of islets in both groups of KO mice, possibly reflecting the impact of this pathway in postnatal neogenesis as suspected in transgenic mice overexpressing a dominant negative GIP receptor. Recent studies have demonstrated the expression and secretion of GIP and GLP-1 in islets. Using specific antibodies, we consistently observed co-localisation of GIP, GLP1, PC2 and PC1/3 together with glucagon in the alpha cells of normal as well as incretin receptor knockout mice. Knockout of GLP-1R resulted in compensatory increases in both pancreatic GIP and GLP-1, whereas abolition of GIPR increased pancreatic GIP. Interestingly, GLP-1R knockout mice exhibited a substantial increase in peripherally located islet cells which were either GLP-1 or GIP positive but glucagon deficient. GIPR KO mice similarly displayed substantial numbers of GLP-1 positive, glucagon deficient islet cells. The decrease of GLP-1/glucagon colocalization in alpha cells of GLP1RKO and GIPRKO mice suggests that these incretin producing cells are derived from alpha cells. Indeed, there is evidence for a switch from PC2 to PC1/3 in islets exposed to increased functional demand or cytotoxic insult. Taken together, these observations in normal and knockout mice suggest that paracrine and other intra-islet effects of locally produced GIP and GLP-1 are likely to exert significant effects given their established actions on islet cell function. In contrast to the pancreas, few comprehensive observations have been made on the intestines of GLP-1R or GIPRKO mice. We observed that impairment of GLP-1R signalling decreased villus length, intestinal L cell count and GLP-1 content, with the expected compensatory increases of intestinal and circulating GIP. On the other hand, GIPRKO mice exhibited decreases in villus length, intestinal K and L cell counts and intestinal GLP-1 content, with paradoxical increase in circulating GIP. Others have reported normal or slightly elevated circulating GIP concentrations. Thus, these data indicate that both GLP-1 and GIP are intimately involved in maintenance and function of incretinproducing enteroendocrine cell populations. It also appears that lack of functional GLP-1 is well compensated by enhancement of GIP, whereas compromised GIP action was not met with increases in circulating GLP-1. As expected, pregnancy induced notable changes in the islet parameters of C57BL/6 mice, with increases in islet area, numbers of medium and large sized islets, beta cell area and both pancreatic and circulating insulin. Pregnancy did not affect alpha cell area, pancreatic glucagon content or islet number, indicating that pregnancy was associated with expansion of beta cell mass.