抄録
In a model of early-stage type II diabetes, we investigated whether angiogenic factors increase the percentage of smaller longitudinal capillaries and interconnecting anastomoses in skeletal muscle, thereby "derecruiting" capillaries through which red blood cells (RBCs) pass, thus accounting for the development of insulin resistance in muscle. The OLETF rat model of type II diabetes was used, with LETO rats as controls. By 16 weeks of age, OLETF rats had developed higher body weights and insulin levels. The RBC velocity (VRBC) in soleus muscle capillaries, measured by intravital microscopy, was significantly higher in OLETF rats. The three-dimensional architecture of the soleus muscle microvessels, visualized by confocal laser-scanning microscopy, showed a higher percentage of longitudinal capillaries and interconnecting anastomoses with luminal diameters < 3 μm in OLETF rats. Real-time PCR showed that OLETF rats had higher messenger RNA levels for the angiogenic factors, VEGF, KDR, Flk-1, angiopoietin-1, and Tie-2. They also had higher levels of VEGF protein, as measured by an enzyme-linked immunosorbent assay. In the presence of increased levels of angiogenic factors, the skeletal muscle microcirculation developed greater numbers of small capillaries and anastomoses during the early stages of diabetes; this reduced the number of capillaries carrying RBCs and increased the velocity of flow in those that continued to transport these cells. [J Physiol Sci. 2007;57 Suppl:S209]
