Dual effects of hyperglycemia on endothelial cells and cardiomyocytes to enhance coronary LPL activity.

In the diabetic heart, there is excessive dependence on fatty acid (FA) utilization to generate ATP. Lipoprotein lipase (LPL)-mediated hydrolysis of circulating triglycerides is suggested to be the predominant source of FA for cardiac utilization during diabetes. In the heart, the majority of LPL is synthesized in cardiomyocytes and secreted onto cell surface heparan sulfate proteoglycan (HSPG), where an endothelial cell (EC)-releasable β-endoglycosidase, heparanase cleaves the side chains of HSPG to liberate LPL for its onward movement across the EC.

Heparanase Overexpression Induces Glucagon Resistance and Protects Animals From Chemically Induced Diabetes.

Heparanase, a protein with enzymatic and nonenzymatic properties, contributes toward disease progression and prevention. In the current study, a fortuitous observation in transgenic mice globally overexpressing heparanase (hep-tg) was the discovery of improved glucose homeostasis. We examined the mechanisms that contribute toward this improved glucose metabolism.