The Role of Glucosamine-Induced ER Stress in Diabetic Atherogenesis

Figure 3

Working model of diabetes-associated accelerated atherothrombosis. Chronic hyperglycemia leads to increased flux through the hexosamine biosynthesis pathway (HBP) resulting in accumulation of UDP-N-acetylglucosamine (UDP-GlcNAc), a substrate for both O- and N-linked protein glycosylation, as well as increased levels of ER stress. Disruptions in ER homeostasis lead to activation of the unfolded protein response (UPR) and downstream effects including activation of glycogen synthase kinase (GSK)-3. Our results suggest that ER-stress-induced GSK-3 induces proatherogenic processes leading to the accelerated development of atherothrombosis.