Figure 4.

A model of the cellular and molecular mechanisms leading to cell proliferation, inflammation, and thrombosis characteristically seen in the target organs of diabetic complications. High levels of glucose in diabetes glycates and thereby inactivates CD59 and also increases complement activation. Combined, these effects of hyperglycemia on the complement system trigger more MAC deposition on cell membranes. The figure illustrates the different cellular signaling pathways induced by high glucose; the complement/MAC-dependent mechanisms summarized in this review are shown on the right, and the complement-independent mechanisms (reviewed in Refs. 5 and 7) are shown on the left. The center of the figure highlights the common signaling pathways reportedly triggered by either high glucose or the MAC. The evidence summarized in this review indicates that both mechanisms are operative in the pathogenesis of diabetes complications.