Dichotomic role of heparanase in a murine model of metabolic syndrome

Esther Hermano, Françoise Carlotti, Alexia Abecassis, Amichay Meirovitz, Ariel M. Rubinstein, Jin Ping Li, Israel Vlodavsky, Ton J. Rabelink, Michael Elkin

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Heparanase is the predominant enzyme that cleaves heparan sulfate, the main polysaccharide in the extracellular matrix. While the role of heparanase in sustaining the pathology of autoimmune diabetes is well documented, its association with metabolic syndrome/type 2 diabetes attracted less attention. Our research was undertaken to elucidate the significance of heparanase in impaired glucose metabolism in metabolic syndrome and early type 2 diabetes. Here, we report that heparanase exerts opposite effects in insulin-producing (i.e., islets) vs. insulin-target (i.e., skeletal muscle) compartments, sustaining or hampering proper regulation of glucose homeostasis depending on the site of action. We observed that the enzyme promotes macrophage infiltration into islets in a murine model of metabolic syndrome, and fosters β-cell-damaging properties of macrophages activated in vitro by components of diabetogenic/obese milieu (i.e., fatty acids). On the other hand, in skeletal muscle (prototypic insulin-target tissue), heparanase is essential to ensure insulin sensitivity. Thus, despite a deleterious effect of heparanase on macrophage infiltration in islets, the enzyme appears to have beneficial role in glucose homeostasis in metabolic syndrome. The dichotomic action of the enzyme in the maintenance of glycemic control should be taken into account when considering heparanase-targeting strategies for the treatment of diabetes.

Original languageEnglish
Pages (from-to)2771-2780
Number of pages10
JournalCellular and Molecular Life Sciences
Issue number6
StatePublished - 1 Mar 2021
Externally publishedYes


  • Diabetes
  • Heparanase
  • Insulin resistance
  • Macrophages
  • Obesity

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology


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