TY  - JOUR
A1  - Van Steenbergen, Anne
A1  - Balteau, Magali
A1  - Ginion, Audrey
A1  - Ferté, Laura
A1  - Battault, Sylvain
A1  - de Meester de Ravenstein, Christophe
A1  - Balligand, Jean-Luc
A1  - Daskalopoulos, Evangelos-Panagiotis
A1  - Gilon, Patrick
A1  - Despa, Florin
A1  - Despa, Sanda
A1  - Vanoverschelde, Jean-Louis
A1  - Horman, Sandrine
A1  - Koepsell, Hermann
A1  - Berry, Gerard
A1  - Hue, Louis
A1  - Bertrand, Luc
A1  - Beauloye, Christophe
T1  - Sodium-myoinositol cotransporter-1, SMIT1, mediates the production of reactive oxygen species induced by hyperglycemia in the heart
JF  - Scientific Reports
N2  - 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.
KW  - hyperglycemia
KW  - Sodium-myoinositol cotransporter-1 (SMIT1)
KW  - glucose metabolism
KW  - heart
KW  - NADPH oxidase 2 (NOX2)
KW  - sodium/glucose cotransporters (SGLT)
KW  - cardiomyocytes
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-180891
VL  - 7
ER  -