Sodium-myoinositol cotransporter-1, SMIT1, mediates the production of reactive oxygen species induced by hyperglycemia in the heart | Zendy

Anne Van Steenbergen | Zendy; Magali Balteau | Zendy; Audrey Ginion | Zendy; Laura Ferté | Zendy; Sylvain Battault | Zendy; Christophe de Meester | Zendy; JeanLuc Balligand | Zendy; Evangelos-Panagiotis Daskalopoulos | Zendy; Patrick Gilon | Zendy; Florin Despa | Zendy; Sanda Despa | Zendy; JeanLouis Vanoverschelde | Zendy; Sandrine Horman | Zendy; Hermann Koepsell | Zendy; Gerard T. Berry | Zendy; Louis Hue | Zendy; Luc Bertrand | Zendy; Christophe Beauloye | Zendy

Open Access

Sodium-myoinositol cotransporter-1, SMIT1, mediates the production of reactive oxygen species induced by hyperglycemia in the heart

Author(s) -

Anne Van Steenbergen,

Magali Balteau,

Audrey Ginion,

Laura Ferté,

Sylvain Battault,

Christophe de Meester,

JeanLuc Balligand,

Evangelos-Panagiotis Daskalopoulos,

Patrick Gilon,

Florin Despa,

Sanda Despa,

JeanLouis Vanoverschelde,

Sandrine Horman,

Hermann Koepsell,

Gerard T. Berry,

Louis Hue,

Luc Bertrand,

Christophe Beauloye

Publication year - 2017

Publication title -

scientific reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.24

H-Index - 213

ISSN - 2045-2322

DOI - 10.1038/srep41166

Subject(s) - nadph oxidase , reactive oxygen species , cotransporter , medicine , gene isoform , endocrinology , chemistry , downregulation and upregulation , diabetic cardiomyopathy , sodium , cardiomyopathy , biochemistry , biology , heart failure , gene , organic chemistry

Hyperglycemia (HG) stimulates the production of reactive oxygen species in the heart through activation of NADPH oxidase 2 (NOX2). This production is independent of glucose metabolism but requires sodium/glucose cotransporters (SGLT). Seven SGLT isoforms (SGLT1 to 6 and sodium-myoinositol cotransporter-1, SMIT1) are known, although their expression and function in the heart remain elusive. We investigated these 7 isoforms and found that only SGLT1 and SMIT1 were expressed in mouse, rat and human hearts. In cardiomyocytes, galactose (transported through SGLT1) did not activate NOX2. Accordingly, SGLT1 deficiency did not prevent HG-induced NOX2 activation, ruling it out in the cellular response to HG. In contrast, myo-inositol (transported through SMIT1) reproduced the toxic effects of HG. SMIT1 overexpression exacerbated glucotoxicity and sensitized cardiomyocytes to HG, whereas its deletion prevented HG-induced NOX2 activation. In conclusion, our results show that heart SMIT1 senses HG and triggers NOX2 activation. This could participate in the redox signaling in hyperglycemic heart and contribute to the pathophysiology of diabetic cardiomyopathy.

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