title: Inhibition of SGLT1 abrogates preconditioning-induced cardioprotection against ischemia-reperfusion injury.
abstract: BACKGROUND
  Recently, we reported Na+/glucose co-transporter (SGLT1) expression in mouse and human heart. We speculated that SGLT1 might play an important role in ischemic preconditioning-induced cardioprotection. Therefore, the present study was designed to find the role of SGLT1 in ischemic preconditioning-induced cardioprotection.
  
  
  METHODS
  Hearts isolated from SD male rats were subjected to either ischemia-reperfusion injury (I/R) (15 min global ischemia followed by 20 min reperfusion) or ischemic preconditioning (IPC) (3 cycles of 2 min global ischemia separated by 3 min reperfusion) followed by I/R in presence and absence of phlorizin, an SGLT1 inhibitor.
  
  
  RESULTS
  IPC increased membrane SGLT1 expression in rat heart as observed by immunoblotting and immunohistochemistry. Hearts from I/R group showed significant increase in oxidative stress levels and marked myocardial injury as compared to control. We also observed significant increase in apoptotic parameters in I/R heart, as measured by caspase-3 activity, TUNEL positive nuclei and gene expression analysis. Significant improvement in oxidative stress, apoptosis parameters and cardiac injury was observed in I/R hearts when subjected to IPC. However, all beneficial effects of preconditioning were lost when hearts were pre-treated with phlorizin.
  
  
  CONCLUSIONS
  Present study indicated that inhibition of SGLT1 by phlorizin abrogated the beneficial effect of ischemic-preconditioning and for the first time, provides evidence that SGLT1 plays a crucial role in ischemic preconditioning-induced cardioprotection.
authors.affiliation: Division of Medicinal Chemistry and Pharmacology, Indian Institute of Chemical Technology, Hyderabad, India; Centre for Pharmaceutical Sciences, JNTU, Hyderabad, India.
authors.forename: Abhinav
authors.initials: A
authors.lastname: Kanwal
authors.forename: Hina L
authors.initials: HL
authors.lastname: Nizami
authors.affiliation: Department of Pathology, National Institute of Nutrition, Hyderabad, India.
authors.forename: Surekha
authors.initials: S
authors.lastname: Mallapudi
authors.affiliation: Department of Pathology, National Institute of Nutrition, Hyderabad, India.
authors.forename: Uday Kumar
authors.initials: UK
authors.lastname: Putcha
authors.affiliation: Centre for Pharmaceutical Sciences, JNTU, Hyderabad, India.
authors.forename: G Krishna
authors.initials: GK
authors.lastname: Mohan
authors.affiliation: Division of Medicinal Chemistry and Pharmacology, Indian Institute of Chemical Technology, Hyderabad, India. Electronic address: skbanerjee@thsti.res.in.
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Banerjee
mesh_terms: D000818:Animals; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology* / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051269:Sodium-Glucose Transporter 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: C495676:Slc5a1 protein, rat; D051269:Sodium-Glucose Transporter 1
keywords: Ischemia-reperfusion injury; Oxidative stress; Phlorizin; Preconditioning; SGLT1