SGLT1 is a novel cardiac glucose transporter that is perturbed in disease states

Abstract

Our data suggest that cardiac SGLT1 expression and/or function are regulated by insulin and leptin, and are perturbed in disease. This is the first study to examine the regulation of cardiac SGLT1 expression by insulin and leptin and to determine changes in SGLT1 expression in cardiac disease.

Interaction of the Sodium/Glucose Cotransporter (SGLT) 2 inhibitor Canagliflozin with SGLT1 and SGLT2

“…In the heart, SGLT1 mRNA was detected in cardiomyocytes by in situ hybridization (Zhou et al, 2003), and SGLT1 protein was localized to the cardiac myocyte sarcolemma (Banerjee et al, 2009). SGLT1 expression levels were increased in diabetic or ischemic cardiomyopathy (Banerjee et al, 2009).…”

Phlorizin Prevents Electrically-Induced Ventricular Tachyarrhythmia during Ischemia in Langendorff-Perfused Guinea-Pig Hearts

“…Thus, the peroxynitrite-scavenging effects of 2-MPG and phlorizin on ventricular muscle during ischemia might not be sufficient to inhibit Ca 2+ overload leading to VT induction in this model. While SGLT1 is expressed in human and mouse cardiomyocytes and its expression is increased in the setting of myocardial ischemia, 17,18) such expression has not yet been demonstrated in guinea pig hearts. Moreover, we failed to demonstrate the expression of SGLT1 using RT-PCR (data not shown).…”

Glucose and Lipid Transporters Roles in Type 2 Diabetes

“…SGLT2 handles the bulk of glucose absorption, 90% of filtered glucose, and has more selectivity in expression, making it the primary target for the majority of inhibitor drugs [2,4,5]. Substrates of SGLT1 include glucose, galactose, and urea, and substrates of SGLT2 include only glucose [6,7]. After absorption by SGLT, glucose exits the cell through solute carrier family 2 facilitated glucose transport member 2 (GLUT2), entering the bloodstream and increasing blood glucose concentration 2 ( Figure 2).…”

“…In type 2 diabetes mellitus (T2DM) patients, SGLT1 was found to be increasingly expressed in certain studies. 1,5,24 In addition, increased glucose uptake in cardiomyocytes following stimulation caused by insulin and leptin signaling illustrates how insulin and leptin may be partly responsible for either SGLT1 expression or translocation to the membrane, as well as increased glucose uptake activity [6,7]. Two laboratories reported partially contradicting results in SGLT1 kidney tissue expression, with the first [8] identifying that SGLT1 expression in T2DM patients is higher than in control patients and the second reporting the same or lower expression of SGLT1/2 and GLUT1/2 when the T2DM patients were compared to the control patients.…”