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Cystathionine‐γ‐lyase (CSE) activation and H2S formation mediate the effect of vitamin D on glucose transporter 4 (GLUT4) translocation and glucose utilization in high glucose treated 3T3L1 adipocytes
Author(s) -
Manna Prasenjit,
Jain Sushil K.
Publication year - 2013
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.27.1_supplement.1010.14
Subject(s) - glut4 , glucose transporter , medicine , endocrinology , chromosomal translocation , glucose uptake , chemistry , carbohydrate metabolism , gene knockdown , insulin , biochemistry , biology , apoptosis , gene
This study examined the biochemical mechanism by which vitamin D supplementation may regulate glucose metabolism in diabetes. 3T3L1 adipocytes were treated with high glucose (HG, 25 mM) in the presence or absence of 1,25‐dihydroxyvitamin D3 [1,25(OH)2D3] (25 or 50 nM), the active form of vitamin D. 1,25(OH)2D3‐treatment up‐regulated GLUT4 translocation, glucose uptake as well as glucose utilization, CSE activation and H2S formation in HG‐treated adipocytes. CSE catalyzes the H2S formation. The effect of 1,25(OH)2D3 on GLUT4 translocation, glucose utilization, and H2S formation was prevented by propargylglycine (an inhibitor of CSE) or in CSE‐knockdown (using antisense CSE) adipocytes compared to controls. 1,25(OH)2D3 treatment along with insulin enhanced GLUT4 translocation and glucose utilization compared to either insulin or 1,25(OH)2D3 alone in HG‐treated cells. 1,25(OH)2D3 supplementation also inhibited MCP‐1 and stimulated adiponectin secretion in HG‐treated adipocytes and this positive effect was prevented in CSE‐inhibitor‐treated or CSE‐knockdown adipocytes. These results demonstrate the essential role of CSE activation and H2S formation in mediating the effect of vitamin D on GLUT4 translocation, glucose utilization, and decrease in inflammatory markers in HG‐treated adipocytes. (Supported by NIDDK RO1 DK072433)