Sodium-dependent glucose transporters (SGLT) in human ischemic heart: A new potential pharmacological target.
BACKGROUND
Empagliflozin is reported to reduce cardiovascular mortality and the rate of hospitalization for heart failure in type 2 diabetic patients with prior cardiovascular events. The mechanisms underlying the cardiac effects of this sodium/glucose transporter 2 (SGT2) inhibitor have not yet been clarified, though a direct action of the drug on the cardiomyocytes could be hypothesized. The aim of the present study is to assess the relative expression of SGLT2 and SGLT1, the two most relevant members of the SGLT family being potentially responsive to empagliflozin, in normal, ischemic and hypertrophic human hearts.


METHODS
Tissue biopsies of healthy (n=9), ischemic (n=9) and hypertrophic (n=6) human hearts were analyzed by real time quantitative RT-PCR, confocal immunofluorescence and Western blot techniques.


RESULTS
We found no expression of SGLT2 in either normal or pathological conditions, whereas SGLT1 was expressed in normal myocardial tissue and significantly upregulated in ischemia and hypertrophy, in association with increased phosphorylation in activating domains of the intracellular second messengers AMP-activated protein kinase (AMPK), extracellular-signal regulated kinase 1 and 2 (ERK-1/2) and mammalian target of rapamycin (mTOR).


CONCLUSIONS
These findings open the possibility that hyperexpressed SGLT1 in cardiomyocytes may represent a potential pharmacological target for cardioprotection.
['Di Franco|Alessandra|A|', 'Cantini|Giulia|G|', 'Tani|Alessia|A|', 'Coppini|Raffaele|R|', 'Zecchi-Orlandini|Sandra|S|', 'Raimondi|Laura|L|', 'Luconi|Michaela|M|', 'Mannucci|Edoardo|E|']
D002478:Cells, Cultured D004730:Endothelium, Vascular D006801:Humans D017202:Myocardial Ischemia D009206:Myocardium D032383:Myocytes, Cardiac D051269:Sodium-Glucose Transporter 1 D051297:Sodium-Glucose Transporter 2
Empagliflozin Heart failure SGLT2 SGLT1 Cardiac hypertrophy Ischemic heart disease Myocardial disease