Abstract
Diabetes is a complex disorder responsible for the mortality and morbidity of millions
of individuals worldwide. Although many approaches have been used to understand and
treat diabetes, the role of proteoglycans, in particular heparan sulfate proteoglycans
(HSPGs), has only recently received attention. The HSPGs are heterogeneous, highly
negatively charged, and are found in all cells primarily attached to the plasma membrane
or present in the extracellular matrix (ECM). HSPGs are involved in development, cell
migration, signal transduction, hemostasis, inflammation, and antiviral activity,
and regulate cytokines, chemokines, growth factors, and enzymes. Hyperglycemia, accompanying
diabetes, increases reactive oxygen species and upregulates the enzyme heparanase
that degrades HSPGs or affects the synthesis of the HSPGs altering their structure.
The modified HSPGs in the endothelium and ECM in the blood vessel wall contribute
to the nephropathy, cardiovascular disease, and retinopathy seen in diabetes. Besides
the blood vessel, other cells and tissues in the heart, kidney, and eye are affected
by diabetes. Although not well understood, the adipose tissue, intestine, and brain
also reveal HSPG changes associated with diabetes. Further, HSPGs are significantly
involved in protecting the β cells of the pancreas from autoimmune destruction and
could be a focus of prevention of type I diabetes. In some circumstances, HSPGs may
contribute to the pathology of the disease. Understanding the role of HSPGs and how
they are modified by diabetes may lead to new treatments as well as preventative measures
to reduce the morbidity and mortality associated with this complex condition.
Keywords
diabetes - heparan sulfate proteoglycans - heparanase
