QSP Modeling Shows Pathological Synergism Between Insulin Resistance and Amyloid-Beta Exposure in Upregulating VCAM1 Expression at the BBB Endothelium.

ABSTRACT: Type 2 diabetes mellitus (T2DM), characterized by insulin resistance, is closely associated with Alzheimer's disease (AD). Cerebrovascular dysfunction is manifested in both T2DM and AD, and is often considered as a pathological link between the two diseases. Insulin signaling regulates critical functions of the blood-brain barrier (BBB), and endothelial insulin resistance could lead to BBB dysfunction, aggravating AD pathology. However, insulin signaling is intrinsically dynamic and involves interactions among numerous molecular mediators. Hence, a mechanistic systems biology model is needed to understand how insulin regulates BBB physiology and the consequences of its impairment in T2DM and AD. In this study, we investigated the pharmacodynamic effect of insulin on the expression of vascu

SUBMITTER: Wang Z 

PROVIDER: S-EPMC11919260 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature