Microcirculation in native and transplanted rodent pancreatic islets with special reference to the influence of diabetes mellitus

Sammanfattning: The aim of the present work was to characterize the islet microcirculation in animal models of type 1 and type 2 diabetes, as well as in islets transplanted to diabetic or normoglycemic recipients. For this purpose, a microsphere technique was evaluated and applied for measurements of islet blood flow in mice.Furthermore, micropuncture techniques for measurements of hydrostatic pressure and tissue oxygen tensionwere adapted to native and transplanted islets. Islet blood flow in normal mice was 1.5-2.5 µl x min-1 x mg estimated islet weight-1. The capillary pressure in native pancreatic islets of rats was ≈3 mm Hg. Obese-hyperglycemic mice demonstrated an jncreased islet blood perfusion, presumably due to leptin-deficiency at 1 month of age, and a decreased islet blood perfusion induced by persistent hyperglycemia at 6-7 months of age, when compared with age-matched lean mice. GK rats, another animal model of type 2 diabetes, displayed a hyperglycemia-dependent increased islet blood flow and islet capillary pressureat ≈15 weeks of age. The present findings suggest that disturbances in islet microcirculation may contribute to the decline in β-cell function seen in type 2 diabetes. An increased islet blood perfusion was also seen in the prediabetic phase in female NOD mice, an animal model of type 1 diabetes. This increase was probably due to an excessive production of nitric oxide. The increased islet blood flow may augment homing of inflammatory cells and soluble factors involved in β-cell destruction to the pancreatic islets during the development of type 1 diabetes in this animal model. The capillary pressure in syngeneic rat islets implanted beneath the kidney capsule approached that of capillaries in the kidney, i.e. 3-4 times higher than in native islets. In diabetic recipients, the graft capillary pressure was higher than in control animals, and was associated with an increased blood flow, as measured by a combination of microspheres and an ultrasonic flow probe. This increase in graft blood flow was not seen when using the laser-Doppler technique. With both techniques the blood perfusion of the grafts was markedly lower than that of the adjacent kidney cortex or native pancreatic islets. The grafts, especially in diabetic recipients, also demonstrated a markedly lower tissue oxygen tension after revascularization than native islets. The latter results are suggestive of an insufficient and inadequate engraftment of transplanted pancreatic islets. This may be of importance for the failures of islet grafts to cure diabetes.