Islet blood flow in multiple low dose streptozotocin-treated wild-type andinducible nitric oxide synthase-deficient mice

The present study tested the hypothesis that changes in islet blood perfusi on occur during the development of diabetes in the multiple low dose strept ozotocin-treated mouse. Streptozotocin (40 mg/kg) or citrate buffer was giv en ip once daily for 5 consecutive days to wildtype and inducible nitric ox ide synthase (iNOS)-deficient C57BL/6 x 129 SvEv hybrid mice. The blood flo ws were then determined by a microsphere technique. The islet blood perfusi on was almost a-fold higher in wild-type mice treated with streptozotocin t han in those given vehicle. Whole pancreatic blood flow was also increased in the streptozotocin-treated wild-type mice. In iNOS-deficient mice, neith er islet blood flow nor whole pancreatic blood flow was affected by repeate d streptozotocin treatment. These combined findings suggest an increased is let blood perfusion in the prediabetic stage mediated by an MOS-dependent m echanism. In combination with increased vasopermeability and expression of adhesion molecules on the islet endothelium, as previously described, this increased islet blood flow may be of crucial importance for the recruitment of inflammatory cells into the islets during the development of diabetes i n this animal model. Indeed, an increased degree of insulitis was observed in wildtype mice compared with mice deficient in iNOS as well as a more rap id decrease in islet volume and an earlier debut of manifest diabetes. We a lso describe altered islet blood perfusion in the iNOS-deficient mice durin g basal conditions due to a compensatory increase in constitutive NOS activ ity.