Table 2.

Examples of Mechanisms Implicated in Diabetic Microvascular Disease

Risk factors: Hyperglycemia
Targets: Endothelium, Podocytes, Pericytes, VSMCs
Increased aldose reductase pathway	Protein kinase activation	Increased oxidative stress	Protein glycation	Increased hexosamine pathway
↑Sorbitol: Osmotic cellular damage ↓(Na+ & K+) ATPase activity ↑NADH/NAD+ ↓NADPH	↑VEGF ↑ROS NF-κB activation Inhibition of eNOS activity ↑Endothelin-1	↑ROS	↑AGE Apoptotic death NFκB activation ↑ROS	↑PAI-1 Inhibition of eNOS activity

VSMCs = vascular smooth muscle cells; eNOS = endothelial nitric oxide synthase; NAD = nicotine adenine dinucleotide; NADH = nicotine adenine dinucleotide reduced; NADPH = nicotine adenine dinucleotide phosphate reduced; PAI-1 = plasminogen activator inhibitor-1; ROS = reactive oxygen species; VEGF = vascular endothelial growth factor; other abbreviations as in Table 1.