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Comment
. 2003 Oct;112(7):986-8.
doi: 10.1172/JCI19902.

Diabetes, microvascular complications, and cardiovascular complications: what is it about glucose?

Jane E B Reusch  1
Affiliations
Comment

Diabetes, microvascular complications, and cardiovascular complications: what is it about glucose?

Jane E B Reusch. J Clin Invest. 2003 Oct.

Abstract

Glycemic control is the primary mediator of diabetic microvascular complications and also contributes to macrovascular complications. A new study (see related article beginning on page 1049) reveals a previously unrecognized association between oxidant activation of poly(ADP ribose) polymerase (PARP) and upregulation of known mediators of glycemic injury. Inhibitors of PARP may have potential therapeutic roles in the prevention of diabetic complications.

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Figures

Figure 1
Figure 1
High glucose flux through constitutive glucose transporters on endothelial cells overwhelms the mitochondrial electron transport system. Excess mitochondrial substrate flux results in the generation of reactive oxygen species that cause DNA strand breaks and activation of PARP. PARP ribosylates and inactivates GAPDH, thereby disrupting normal glucose metabolism. Inactivation of GAPDH effectively shunts glucose into the polyol pathway and leads to activation of PKC and accumulation of AGEs and glucosamine. DAG, diacylglycerol.
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