The Sodium-Glucose Co-Transporter 2 Inhibitor, Empagliflozin, Protects against Diabetic Cardiomyopathy by Inhibition of the Endoplasmic Reticulum Stress Pathway

Background/Aims: This study aimed to determine whether or not the sodium-glucose co-transporter 2 inhibitor, empagliflozin (EMPA), can protect against diabetic cardiomyopathy (DCM) and to elucidate the related mechanism. Methods: Rats were divided into the following four groups: a non-diabetic group; diabetic cardiomyopathy rats without EMPA treatment; and diabetic cardiomyopathy rats with EMPA treatment (low- and high-dose EMPA). Hemodynamic measurements were performed to evaluate left ventricular systolic and diastolic function. The histopathology of the heart was examined with hematoxylin-eosin staining. Expression of glucose-regulated protein (GRP)78, enhancer-binding protein homologous protein (CHOP), and caspase-12 was detected by Western blot, and the mRNA levels of XBP1, ATF4, and TRAF2 were analysed by real-time PCR. Results: EMPA significantly decreased the blood glucose level when compared with vehicle. EMPA strongly improved cardiac function based on hemodynamic and histopathologic analyses. Moreover, EMPA can significantly down-regulate the expression of GRP78, CHOP, and caspase-12 (P < 0.01). Additionally, the mRNA levels of XBP1, ATF4, and TRAF2 were markedly decreased by administration of EMPA (P < 0.01). Conclusion: EMPA protects against DCM by inactivating the endoplasmic reticulum stress pathway.

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PPARβ/δ Agonist Provides Neuroprotection by Suppression of IRE1α–Caspase-12-Mediated Endoplasmic Reticulum Stress Pathway in the Rotenone Rat Model of Parkinson’s Disease

Molecular Neurobiology ◽

10.1007/s12035-015-9309-9 ◽

2015 ◽

Vol 53 (6) ◽

pp. 3822-3831 ◽

Cited By ~ 12

Author(s):

Qiang Tong ◽

Liang Wu ◽

Qing Gao ◽

Zhou Ou ◽

Dongya Zhu ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Endoplasmic Reticulum ◽

Endoplasmic Reticulum Stress ◽

Rat Model ◽

Caspase 12 ◽

Endoplasmic Reticulum Stress Pathway ◽

Stress Pathway

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Glucagon-Like Peptide-1 Analog Liraglutide Protects against Diabetic Cardiomyopathy by the Inhibition of the Endoplasmic Reticulum Stress Pathway

Journal of Diabetes Research ◽

10.1155/2013/630537 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 19

Author(s):

Jieyu Liu ◽

Yu Liu ◽

Li Chen ◽

Yuehui Wang ◽

Junqi Li

Keyword(s):

Cardiac Function ◽

Diabetic Cardiomyopathy ◽

Caspase 3 ◽

Mrna Levels ◽

Caspase 12 ◽

Before And After ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Endoplasmic Reticulum Stress Pathway ◽

Stress Pathway

Aim. This study aimed to investigate whether the glucagon-like peptide-1 analog liraglutide (LIRA) can protect against diabetic cardiomyopathy and explore the related mechanism.Methods. Rats were divided into 6 groups: a nondiabetic group, diabetic cardiomyopathy rats without LIRA treatment, diabetic cardiomyopathy rats with LIRA treatment (with high-, medium-, and low-dose, resp.), and diabetic cardiomyopathy rats treated with insulin. Cardiac function was examined by echocardiography before and after treatment. The histopathology of the heart was examined with H&E staining. The mRNA levels of XBP1, ATF4, and TRAF2 were analyzed by RT-PCR, and the expression of glucose-regulated protein 78 (Grp78), enhancer-binding protein homologous protein (CHOP), caspase-3, and caspase-12 was detected by western blot.Results. LIRA strongly improved cardiac function from both echocardiographic and histopathologic analyses, but insulin only partly increased cardiac function by improving FS and LVPW values. LIRA treatment can significantly decrease the expression of XBP1, ATF4, and TRAF2 (P<0.01). LIRA also significantly downregulates the expression of Grp78, caspase-3 (P<0.01), CHOP, and caspase-12 (P<0.05).Conclusions. LIRA can protect against diabetic cardiomyopathy by inactivating the ER stress pathway. The improvement in cardiac function by LIRA is independent of glucose control.

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