Abstract W P252: Amylin Vasculopathy, a Novel Mechanism of Cerebrovascular Injury and Neurologic Deficits in Diabetes

摘要: Human amylin is an amyloidogenic hormone that forms toxic oligomers kill the insulin-producing β-cells in pancreas of patients with type-2 diabetes. We recently showed pancreatic pathology also linked cerebrovascular dementia and diabetic heart disease by increased circulating levels oligomerized amylin. Here, we tested hypothesis accumulation injures brain, leading to neurologic deficits independently hyperglycemia. A rat model overexpressing human (the HIP rat) appropriate controls were used investigate mechanistically effects accumulation. As controls, employed wild-type (WT) littermates age- glucose-matched rats expressing only non-amyloidogenic WT amylin, which does not accumulate or other organs. Compared reduced exploratory drive, vestibulomotor performance recognition memory. Cortical arteries isolated from displayed a ~40% higher myogenic tone (P<0.05), correlates mean arterial blood pressure ~20% (P<0.05). found elevated lipid peroxidation (by 18±3%; P<0.05) activated Ca2+-mediated hypertrophy signaling cortical smooth muscle cells compared control rats. Serial staining ED1 antibody indicates possible microglia/macrophages are clustering vessel areas positive for infiltration. Multiple inflammatory markers expressed brains rats, confirming deposition induces response. Overall, our data suggest associated via mechanisms vascular dysfunction, oxidative stress neuroinflammation.