Endocrine Abstracts

Microcirculatory deterioration can occur early in the development of diabetes and structural changes in the capillary beds are well reported. High levels of insulin have been found to damage blood vessels and, particularly in type 2 diabetes (T2D), are linked to cardiovascular diseases such as hypertension. Therefore, we hypothesised that capillary beds surrounding the islets of Langerhans would also be affected by these vascular changes during the onset and progression of disease. With the use of super-resolution ultrasound (SRUS) it is possible to obtain high resolution (10um) structural and dynamic data on the microvasculature, including blood vessel coverage, vessel diameter, and blood velocity. For this study, we used polygenic T2D Tally Ho mouse model, in which males typically develop diabetes spontaneously around 8 to 10 weeks of age. Fasted male Tally Ho mice were anaesthetised and intravenously infused with a microbubble (MB) contrast agent (790ul/min/kg, IV) while images of the pancreas were acquired. Post processing of the data enabled us to locate and track individual MBs flowing through the microvasculature of the pancreas. These imaging sessions were performed on a weekly basis before and during the onset of glucose intolerance. Fasted blood glucose measurements were also taken on a weekly basis to monitor the progression of T2D. Control mice which did not develop diabetes showed no change in blood flow in the pancreas. Mice that developed diabetes showed a significant negative correlation between blood glucose levels and a pancreatic blood flow. These preliminary results suggest a relationship between a deterioration of the microcirculation in the pancreas and a disruption in glucose homeostasis. SRUS imaging could be used as a non-invasive tool to longitudinally follow the effect of T2D on the microvasculature of the pancreas and provide insight into the mechanisms of the disease and potential drug targets.