Pancreatic-islet microvascular vasomotion dysfunction in mice with spinal cord injury

Abstract

Patients with spinal cord injury (SCI) have an increased risk for developing type 2 diabetes. It is unknown whether the pancreatic-islet microvascular vasomotion is involved. We used female C57BL/6 mice and a 100-kilodyne T10 Infinite Horizons contusion SCI (or T10 laminectomy) to detect blood glucose and pancreatic-islet microvascular vasomotion. Blood glucose obtained from tail vein was detected using one Touch UltraEasy glucometer. Glucose tolerance test was performed by d-glucose administration intraperitoneally. Functional status of pancreatic-islet microvascular vasomotion was determined by laser Doppler monitoring. Expressions of insulin and glucagon were determined by immunohistochemistry. Expression of VEGF-A was determined by immunohistochemistry and Western blotting. Our result demonstrated that blood glucose was significantly increased at 4 h postinjury compared to that in sham group, with continuous higher blood glucose until 4 days postinjury (p < 0.05). SCI mice at day 7 and day 14 had significantly impaired glucose tolerance following glucose administration (p < 0.01). Average blood perfusion, amplitude, frequency, and relative velocity of vasomotion were significantly lower at 6 h postinjury than those in the sham group (p < 0.05), which were gradually upregulated over time. The expression of insulin was decreased, while the expression of glucagon was increased at 6 h postinjury. Similarly, the expression of VEGF-A was significantly decreased at 6 h postinjury, compared to that in sham group (p < 0.05), with slight increases by 14 days postinjury. Our study suggests that the functional status of pancreatic-islet microvascular vasomotion is impaired after injury, which may have implications for developing effective therapeutic interventions for SCI.

Keywords: Blood glucose; Microvascular vasomotion; Spinal cord injury; VEGF-A.