RT Journal Article
SR Electronic
T1 Dapagliflozin Suppresses ER Stress and Improves Subclinical Myocardial Function in Diabetes: from Bedside to Bench
JF Diabetes
JO Diabetes
FD American Diabetes Association
SP db200840
DO 10.2337/db20-0840
A1 Shih, Jhih-Yuan
A1 Lin, Yu-Wen
A1 Fisch, Sudeshna
A1 Cheng, Juei-Tang
A1 Kang, Nai-Wen
A1 Hong, Chon-Seng
A1 Chen, Zhih-Cherng
A1 Chang, Wei-Ting
YR 2020
UL http://diabetes.diabetesjournals.org/content/early/2020/10/27/db20-0840.abstract
AB Dapagliflozin (DAPA) -- a sodium glucose cotransporter 2 (SGLT2) inhibitor, is approved for treatments of diabetic patients. DAPA-HF trial disclosed its benefits in symptomatic heart failure but the underlying mechanism remains largely unknown. In this longitudinal and prospective study, we investigated changes of left ventricular (LV) functions including speckle tracking in diabetic patients free from symptomatic heart failure post DAPA treatment. Using streptozotocin-induce diabetic rat model, we measured the effects of DAPA on myocardial function. In patients with diabetes, following six months of DAPA, despite no significant changes LV ejection fraction, the diastolic function and longitudinal strain improved. Likewise, compared to control, the diabetic rat heart developed pronounced fibrosis, a decline in strain and overall hemodynamics, all of which were mitigated by DAPA treatment. In contrast, despite insulin exerting a glucose lowering effect, it failed to improve myocardial function and fibrosis. In our in vitro study, under high glucose cardiomyocytes showed significant activations of apoptosis, reactive oxygen species and ER stress associated proteins, which were attenuated by the co-incubation of DAPA. Mechanistically, DAPA suppressed ER stress, reduced myocardial fibrosis and improved overall function. The results can lead to further improvement in management of LV function in diabetic patients.