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div>This was reflected by decreased islet numbers in GLP-1R KO mice and decreases in islet size and beta cell area together with increased alpha cell mass in both transgenic mouse models. Knock-out of GLP-1R also resulted in increased pancreatic GLP-1 without change of pancreatic glucagon or circulating hormone levels, suggesting that insulin deficiency and/ or receptor deletion affects cellular GLP-1 production from the proglucagon precursor. In contrast, circulating GIP was decreased in in both groups of receptor knock-out mice without affecting tissue stores. Irrespective of these changes, deletion of receptors for either incretin hormone did not greatly affect the course of severe insulin deficient diabetes. This likely reflects the severe hyperglycaemia and substantial level of damage inflicted on beta cells, as witnessed by lack of beta cell regeneration and markedly decreased Ki67/TUNEL ratios in control BMS-907351 abmole bioscience diabetic C57BL/6 mice. The metabolic and islet cell responses to hydrocortisone treatment were quite different to those induced by multiple low doses of streptozotocin. Thus, C57BL/6 animals exhibited markedly increased islet, beta and alpha cell areas associated with increased numbers of medium and large sized islets. Ki67 proliferation was enhanced and there was only a small level of apoptosis as judged by TUNEL staining. Both pancreatic and plasma levels of insulin but not glucagon were markedly elevated but glucose concentrations were relatively normal, indicating the effectiveness of markedly enhanced beta cell activity to overcome severe insulin resistance. In addition to such metabolic actions on islets, we cannot discount that hydrocortisone might also exert direct effects on the function of beta and alpha cells. Intra-islet expression of GLP-1 and GIP was clearly evident with increased numbers of alpha cells mainly producing GIP. Pancreatic and circulating levels of GLP-1 and GIP were unchanged, thereby excluding a significant role of intestinally-derived hormones in cellular and metabolic effects. Thus, ablation of intra-islet, as opposed to circulating GLP-1 or GIP, actions using receptor KO mice appear to be responsible for loss of the normal compensatory increases of islet numbers and morphology induced by hydrocortisone, with islet size and beta cell mass remarkably less than observed in normal C57BL/6 mice. Numbers of islets in GIPR KO mice were also less than hydrocortisone treated C57BL/6 mice. Accordingly, it appears that the sole or dual additive actions of GLP-1 and GIP produced locally by alpha cells may be particularly important in terms of islet responses to increased functional demand. These combined observations suggest that GLP-1 and GIP produced largely by islet alpha cells may play a hitherto unproven role in islet adaptation to insulin resistance and the control of glucose homeostasis. Further studies using mice with specific knock-out of incretin receptors in islets would be useful to investigate this further. Decreased beta cell mass and inability to secrete appropriate amounts of insulin are classical features of gestational as well as type 1 and type 2 diabetes. Since existing therapies target insulin replacement or enhancing insulin secretion/action, intra-islet production of GLP-1 and GIP through manipulation of proconvertase enzymes may represent a therapeutically useful way to increase beta cell mass and physiological insulin secretion. Schistosomiasis is a helminth disease that affects more than 200 million people predominantly in developing countries. Schistosoma mansoni infection is a long lasting inflammatory reaction characterized by the presence of adult worms living in the mesenteric venous system, depositing their eggs in small submucosal veins of the intestine. Some of these eggs are washed through the portal blood flow into the liver, where they cause granulomatous inflammatory reactions. A typical Th2 response is well defined in the acute phase and the evolution towards the chronic phase is associated with a down-regulation of several aspects of the immune response to parasites. Egg and worm antigens are continuously drained to mesenteric lymph nodes, where they induce an intense polyclonal B cell activation and germinal center reaction in the lymphoid follicles, concomitant with development of splenomegaly. Lymph nodes have a well-defined lymphoid architecture: a cortical regi