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Dichotomic role of ...
Dichotomic role of heparanase in a murine model of metabolic syndrome
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- Hermano, Esther (författare)
- Hadassah Hebrew Univ, Med Ctr, Sharett Inst, Dept Oncol, IL-91120 Jerusalem, Israel.
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- Carlotti, Francoise (författare)
- Leiden Univ, Med Ctr, Dept Internal Med, Div Nephrol, Leiden, Netherlands.
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- Abecassis, Alexia (författare)
- Hadassah Hebrew Univ, Med Ctr, Sharett Inst, Dept Oncol, IL-91120 Jerusalem, Israel.
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- Meirovitz, Amichay (författare)
- Hadassah Hebrew Univ, Med Ctr, Sharett Inst, Dept Oncol, IL-91120 Jerusalem, Israel.
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- Rubinstein, Ariel M. (författare)
- Hadassah Hebrew Univ, Med Ctr, Sharett Inst, Dept Oncol, IL-91120 Jerusalem, Israel.
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- Li, Jin-Ping (författare)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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- Vlodavsky, Israel (författare)
- Technion, Rappaport Fac Med, Canc & Vasc Biol Res Ctr, Haifa, Israel.
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- Rabelink, Ton J. (författare)
- Leiden Univ, Med Ctr, Dept Internal Med, Div Nephrol, Leiden, Netherlands.
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- Elkin, Michael (författare)
- Hadassah Hebrew Univ, Med Ctr, Sharett Inst, Dept Oncol, IL-91120 Jerusalem, Israel.;Hebrew Univ Jerusalem, Med Sch, IL-91120 Jerusalem, Israel.
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Hadassah Hebrew Univ, Med Ctr, Sharett Inst, Dept Oncol, IL-91120 Jerusalem, Israel Leiden Univ, Med Ctr, Dept Internal Med, Div Nephrol, Leiden, Netherlands. (creator_code:org_t)
- 2020-10-13
- 2021
- Engelska.
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Ingår i: Cellular and Molecular Life Sciences (CMLS). - : Springer. - 1420-682X .- 1420-9071. ; 78, s. 2771-2780
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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 beta-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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Nyckelord
- Heparanase
- Diabetes
- Obesity
- Macrophages
- Insulin resistance
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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