Endothelial heparanase secretion after acute hypoinsulinemia is regulated by glucose and fatty acid

Fang Wang, Min Suk Kim, Prasanth Puthanveetil, Girish Kewalramani, Sylvia Deppe, Sanjoy Ghosh, Ashraf Abrahani, Brian Rodrigues

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42 Scopus citations


Following diabetes, the heart increases its lipoprotein lipase (LPL) at the coronary lumen by transferring LPL from the cardiomyocyte to the endothelial lumen. We examined how hyperglycemia controls secretion of heparanase, the enzyme that cleaves myocyte heparan sulphate proteoglycan to initiate this movement. Diazoxide (DZ) was used to decrease serum insulin and generate hyperglycemia. A modified Langendorff technique was used to separate coronary from interstitial effluent, which were assayed for heparanase and LPL. Within 30 min of DZ, interstitial heparanase increased, an effect that closely mirrored an augmentation in interstitial LPL. Endothelial cells were incubated with palmitic acid (PA) or glucose, and heparanase secretion was determined. PA increased intracellular heparanase, with no effect on secretion of this enzyme. Unlike PA, glucose dose- dependently lowered endothelial intracellular heparanase, which was strongly associated with increased heparanase activity in the incubation medium. Preincubation with cytochalasin D or nocodazole prevented the high glucose-induced depletion of intracellular heparanase. Our data suggest that following hyperglycemia, translocation of LPL from the cardiomyocyte cell surface to the apical side of endothelial cells is dependent on the ability of the fatty acid to increase endothelial intracellular heparanase followed by rapid secretion of this enzyme by glucose, which requires an intact microtubule and actin cytoskeleton.

Original languageEnglish
Pages (from-to)H1108-H1116
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number4
StatePublished - Apr 2009


  • Cytoskeleton
  • Diabetes
  • Diazoxide
  • Endothelial cell
  • High glucose


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