GLP-1 Cleavage Product Reverses Persistent ROS Generation After Transient Hyperglycemia by Disrupting an ROS-Generating Feedback Loop.

ABSTRACT: The assumption underlying current diabetes treatment is that lowering the level of time-averaged glucose concentrations, measured as HbA1c, prevents microvascular complications. However, 89% of variation in risk of retinopathy, microalbuminuria, or albuminuria is due to elements of glycemia not captured by mean HbA1c values. We show that transient exposure to high glucose activates a multicomponent feedback loop that causes a stable left shift of the glucose concentration-reactive oxygen species (ROS) dose-response curve. Feedback loop disruption by the GLP-1 cleavage product GLP-1(9-36)(amide) reverses the persistent left shift, thereby normalizing persistent overproduction of ROS and its pathophysiologic consequences. These data suggest that hyperglycemic spikes high enough to activate p

SUBMITTER: Giacco F 

PROVIDER: S-EPMC4542449 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature