The vascular trigger of type II diabetes mellitus.

Type II diabetes mellitus is associated with obesity and insulin resistance. However, many humans with these symptoms never develop diabetes. This raises the key question of the difference that determines why one obese individual develops diabetes, whereas another one does not. Here we review the experimental support for our hypothesis that mutual signaling between insulin producing beta cells and pancreatic endothelial cells determines whether a person develops type II diabetes. According to our hypothesis, a disturbance of this mutual signaling leads to diabetes in an insulin-resistant individual. We discuss that most type II diabetes-associated genes have a function in the vascular system, and that endoplasmic reticulum (ER) stress in beta cells can result from vascular defects in pancreatic islets. Whereas vascular complications have been widely accepted as a result of type II diabetes, we suggest that changes within the vascular system may act at an earlier stage and trigger the onset of type II diabetes.