Abstract 20676: Differential Endomyocardial Expression of SGLT in Idiopathic Dilated Cardiomyopathy Patients With and Without Diabetes Mellitus

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Abstract

Introduction: Although abnormal glucose metabolism in heart failure is related to differential regulation of glucose transporters, the role and expression of Sodium-Glucose cotransporter(SGLT) remains undetermined. Hence more information is required to delineate the exact subtypes of these SGLTs expressed in heart failure.

Aim: To investigate whether in addition to common glucose transporter 1(Glut1) and 4(Glut4), SGLT1 and 2 are expressed in human heart. In addition we hypothesized that the SGLT transcriptional profile in heart failure is altered in patients with diabetes mellitus.

Methods and Results: LV endomyocardial biopsies obtained from 76 patients with heart failure due to idiopathic dilated cardiomyopathy(CMP) (ejection fraction 44±3%; LVEDVI: 115±7 ml/m2 and PCWP 20±1 mm Hg) were analysed for SGLT1, SGLT2, Glut1 and Glut4 mRNA gene expression using quantitative RT-PCR.

Results: Baseline hemodynamic characteristics were similar between DM+ and DM- pts(EF: 43±6 vs 43±3%, p=ns; PCWP 20±2 vs 20±1 mm Hg, p=ns). Whereas no difference in Glut1 and Glut4 mRNA gene expression was observed between both groups(p=ns), DM+ pts were characterized by significantly higher SGLT1 expression compared to DM-pts(0,2391± 0,0280 vs 0,1597 ± 0,0125 rel units; p = 0.007). In both groups SGLT2 endomyocardial mRNA was not detected. A significant correlation was noted between SGLT1 and Glut4 in DM-pts (p<0,0001) which was not the case for DM+ pts (p=0.07).

Conclusion: In addition, to common Glut1 and Glut4, SGLT1 but not SGLT2 plays a role in glucose transport in CMP. The identification of lower SGLT1 gene expression and its direct relationship with Glut4 in DM- vs DM+pts raises the hypothesis that myocardial glucose uptake is differentially regulated in diabetes.

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