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Manganese downregulates ICAM‐1 expression in endothelial cells treated with high glucose
Author(s) -
Burlet Elodie,
Jain Sushil K
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1026.1
Subject(s) - medicine , endocrinology , icam 1 , diabetes mellitus , umbilical vein , adiponectin , secretion , chemistry , cholesterol , insulin resistance , biochemistry , intracellular , in vitro
Diabetes is associated with low levels of manganese (Mn 2+ ), an important component of many enzyme systems. Previous studies in our laboratory have shown that Zucker diabetic fatty rats (ZDF) supplemented with Mn 2+ lower cholesterol, triglycerides, MCP‐1, ICAM‐1 and higher adiponectin levels in blood. This study examined the potential mechanisms by which Mn 2+ supplementation decreases blood cholesterol and triglycerides and atherosclerosis associated with diabetes. Human umbilical vein endothelial cells (HUVECs) were treated with different concentrations of Mn 2+ (0, 5, 10 and 20μM) for 24 hours, then exposed to high glucose (25mM) or MCP‐1 (250pg/mL) for another 24 hrs. ICAM‐1 expression was determined by Western blotting. Our results demonstrate that HG increases ICAM‐1 expression by two fold compared with controls, and that pre‐treatment with 5μM Mn 2+ decreased ICAM‐1 expression back to control levels. Similar experiments with 3T3‐L1 adipocytes showed that pre‐treatment with 10μM Mn 2+ inhibited HG‐induced secretion of MCP‐1 levels to control levels. ICAM‐1 and MCP‐1 are key players in the development of atherosclerosis and CVD in diabetes. This study suggests that Mn 2+ supplementation inhibits MCP‐1 secretion and ICAM‐1 expression, which in turn may lower circulating triglycerides and cholesterol and risk of development of atherosclerosis in diabetes. Supported by NIDDK (RO1 DK072433), Office of Dietary Supplements and Malcolm Feist Chair in Diabetes.