The Experts below are selected from a list of 5949 Experts worldwide ranked by ideXlab platform
Carsten Tschope - One of the best experts on this subject based on the ideXlab platform.
-
kinins in cardiac inflammation and regeneration insights from ischemic and Diabetic Cardiomyopathy
Neuropeptides, 2010Co-Authors: Konstantinos Savvatis, Heinzpeter Schultheiss, Dirk Westermann, Carsten TschopeAbstract:The kallikrein-kinin system (KKS) is a system of vasoactive peptides, the kinins, involved in different aspects of remodeling, inflammation and angiogenesis. Kinins mediate their actions through two receptors, B1R and B2R. It is increasingly recognized that the KKS is involved in the inflammatory processes of the heart. Evidence shows that the B2R is beneficial in myocardial diseases, protecting from inflammation, fibrosis and apoptosis, while B1R shows a proinflammatory character contributing to the disease progression by increasing the production of cytokines and stimulating the migration of immune cells. Furthermore, novel important actions of the KKS and its receptors contribute to neovascularization and recruitment of endothelial progenitor cells in ischemic areas and endothelial dysfunction. The kinin receptors could therefore constitute potential therapeutic targets in the treatment of myocardial ischemia and Diabetic Cardiomyopathy.
-
gene deletion of the kinin receptor b1 attenuates cardiac inflammation and fibrosis during the development of experimental Diabetic Cardiomyopathy
Diabetes, 2009Co-Authors: Dirk Westermann, Heinzpeter Schultheiss, Konstantinos Savvatis, Thomas Walther, Felcicitas Escher, Meike Sobirey, Alexander Riad, Michael Bader, Carsten TschopeAbstract:OBJECTIVE Diabetic Cardiomyopathy is associated with increased mortality in patients with diabetes. The underlying pathology of this disease is still under discussion. We studied the role of the kinin B1 receptor on the development of experimental Diabetic Cardiomyopathy. RESEARCH DESIGN AND METHODS We utilized B1 receptor knockout mice and investigated cardiac inflammation, fibrosis, and oxidative stress after induction of streptozotocin (STZ)-induced diabetes. Furthermore, the left ventricular function was measured by pressure-volume loops after 8 weeks of diabetes. RESULTS B1 receptor knockout mice showed an attenuation of Diabetic Cardiomyopathy with improved systolic and diastolic function in comparison with Diabetic control mice. This was associated with a decreased activation state of the mitogen-activated protein kinase p38, less oxidative stress, as well as normalized cardiac inflammation, shown by fewer invading cells and no increase in matrix metalloproteinase-9 as well as the chemokine CXCL-5. Furthermore, the profibrotic connective tissue growth factor was normalized, leading to a reduction in cardiac fibrosis despite severe hyperglycemia in mice lacking the B1 receptor. CONCLUSIONS These findings suggest that the B1 receptor is detrimental in Diabetic Cardiomyopathy in that it mediates inflammatory and fibrotic processes. These insights might have useful implications on future studies utilizing B1 receptor antagonists for treatment of human Diabetic Cardiomyopathy.
-
development of Diabetic Cardiomyopathy and the kallikrein kinin system new insights from b1 and b2 receptor signaling
Biological Chemistry, 2008Co-Authors: Carsten Tschope, Dirk WestermannAbstract:Diabetic Cardiomyopathy is a specific Cardiomyopathy which develops in patients with diabetes mellitus in the absence of coronary atherosclerosis and hypertension. Despite the potential importance of this disease entity, the underlying mechanisms are only incompletely understood. Changes in calcium handling, disruption of the extracellular matrix regulation with accumulation of cardiac collagen, and furthermore cardiac inflammation may be an important mediator of this disease. This brief review focuses on the current aspects of the kallikrein-kinin system and its influence on the development of Diabetic Cardiomyopathy with particular regard to the kinin receptors B1 and B2, as their role in the development of this disease is still under discussion. Whether the role of the B1 receptor is similar to the well-described beneficial role of the B2 receptor or whether its function is opposed to the B2 receptor is controversial. Some recent findings suggest that the B1 receptor mediates cardiac inflammation and therefore may be detrimental for cardiac function in the setting of Diabetic Cardiomyopathy.
-
transgenic activation of the kallikrein kinin system inhibits intramyocardial inflammation endothelial dysfunction and oxidative stress in experimental Diabetic Cardiomyopathy
The FASEB Journal, 2005Co-Authors: Carsten Tschope, Heinzpeter Schultheiss, Thomas Walther, Michael Bader, Felicitas Escher, Frank Spillmann, Christine Altmann, Ingolf Schimke, Carlos F Sanchezferrer, Michel NoutsiasAbstract:The mechanisms contributing to Diabetic Cardiomyopathy, as well as the protective pathways of the kallikrein-kinin-system (KKS), are incompletely understood. In a kallikrein-overexpressing rat model of streptozotocin (STZ)-induced Diabetic Cardiomyopathy, we investigated the involvement of inflammatory pathways, endothelial dysfunction, and oxidative stress. Six weeks after STZ injection, impairment of left ventricular (LV) function parameters measured by a Millar-tip catheter (peak LV systolic pressure; dP/dtmax; dP/dtmin) was accompanied by a significant increment of ICAM-1 and VCAM-1 (CAMs) expression, as well as of beta2-leukocyte-integrins+ (CD18+, CD11a+, CD11b+) and cytokine (TNF-alpha and IL-1beta)-expressing infiltrates in male Sprague-Dawley (SD-STZ) rats compared with normoglycemic littermates. Furthermore, SD-STZ rats demonstrated a significant impairment of endothelium-dependent relaxation evoked by acetylcholine and significantly increased plasma TBARS (plasma thiobarbituric acid reactive substances) levels as a measure of oxidative stress. These Diabetic Cardiomyopathy-associated alterations were significantly attenuated (P<0.05) in Diabetic transgenic rats expressing the human kallikrein 1 (hKLK1) gene with STZ-induced diabetes. CAMs expression, beta2-leukocyte-integrins+, and cytokine-expressing infiltrates correlated significantly with all evaluated LV function parameters. The multiple protective effects of the KKS in experimental Diabetic Cardiomyopathy comprise the inhibition of intramyocardial inflammation (CAMs expression, beta2-leukocyte-integrins+ infiltration and cytokine expression), an improvement of endothelium-dependent relaxation and the attenuation of oxidative stress. These insights might have therapeutic implications also for human Diabetic Cardiomyopathy.
-
transgenic activation of the kallikrein kinin system inhibits intramyocardial inflammation endothelial dysfunction and oxidative stress in experimental Diabetic Cardiomyopathy
The FASEB Journal, 2005Co-Authors: Carsten Tschope, Thomas Walther, Michael Bader, Felicitas Escher, Frank Spillmann, Christine Altmann, Ingolf Schimke, Carlos F Sanchezferrer, Jing Du, Heinzpeter SchultheissAbstract:SPECIFIC AIMSIn light of the possible involvement of intramyocardial inflammation in Diabetic Cardiomyopathy, we investigated cardiac CAMs expression (ICAM-1 and VCAM-1) and β2-leukocyte integrins+...
M Arow - One of the best experts on this subject based on the ideXlab platform.
-
sodium glucose cotransporter 2 inhibitor dapagliflozin attenuates Diabetic Cardiomyopathy
Cardiovascular Diabetology, 2020Co-Authors: M Arow, Maayan Waldman, Dor Yadin, Vadim Nudelman, Asher Shainberg, Nader G Abraham, Dov FreimarkAbstract:Diabetes mellitus type 2 (DM2) is a risk factor for developing heart failure but there is no specific therapy for Diabetic heart disease. Sodium glucose transporter 2 inhibitors (SGLT2I) are recently developed Diabetic drugs that primarily work on the kidney. Clinical data describing the cardiovascular benefits of SGLT2Is highlight the potential therapeutic benefit of these drugs in the prevention of cardiovascular events and heart failure. However, the underlying mechanism of protection remains unclear. We investigated the effect of Dapagliflozin—SGLT2I, on Diabetic Cardiomyopathy in a mouse model of DM2. Cardiomyopathy was induced in Diabetic mice (db/db) by subcutaneous infusion of angiotensin II (ATII) for 30 days using an osmotic pump. Dapagliflozin (1.5 mg/kg/day) was administered concomitantly in drinking water. Male homozygous, 12–14 weeks old WT or db/db mice (n = 4–8/group), were used for the experiments. Isolated cardiomyocytes were exposed to glucose (17.5–33 mM) and treated with Dapagliflozin in vitro. Intracellular calcium transients were measured using a fluorescent indicator indo-1. Angiotensin II infusion induced Cardiomyopathy in db/db mice, manifested by cardiac hypertrophy, myocardial fibrosis and inflammation (TNFα, TLR4). Dapagliflozin decreased blood glucose (874 ± 111 to 556 ± 57 mg/dl, p < 0.05). In addition it attenuated fibrosis and inflammation and increased the left ventricular fractional shortening in ATII treated db/db mice. In isolated cardiomyocytes Dapagliflozin decreased intracellular calcium transients, inflammation and ROS production. Finally, voltage-dependent L-type calcium channel (CACNA1C), the sodium–calcium exchanger (NCX) and the sodium–hydrogen exchanger 1 (NHE) membrane transporters expression was reduced following Dapagliflozin treatment. Dapagliflozin was cardioprotective in ATII-stressed Diabetic mice. It reduced oxygen radicals, as well the activity of membrane channels related to calcium transport. The cardioprotective effect manifested by decreased fibrosis, reduced inflammation and improved systolic function. The clinical implication of our results suggest a novel pharmacologic approach for the treatment of Diabetic Cardiomyopathy through modulation of ion homeostasis.
Heinzpeter Schultheiss - One of the best experts on this subject based on the ideXlab platform.
-
kinins in cardiac inflammation and regeneration insights from ischemic and Diabetic Cardiomyopathy
Neuropeptides, 2010Co-Authors: Konstantinos Savvatis, Heinzpeter Schultheiss, Dirk Westermann, Carsten TschopeAbstract:The kallikrein-kinin system (KKS) is a system of vasoactive peptides, the kinins, involved in different aspects of remodeling, inflammation and angiogenesis. Kinins mediate their actions through two receptors, B1R and B2R. It is increasingly recognized that the KKS is involved in the inflammatory processes of the heart. Evidence shows that the B2R is beneficial in myocardial diseases, protecting from inflammation, fibrosis and apoptosis, while B1R shows a proinflammatory character contributing to the disease progression by increasing the production of cytokines and stimulating the migration of immune cells. Furthermore, novel important actions of the KKS and its receptors contribute to neovascularization and recruitment of endothelial progenitor cells in ischemic areas and endothelial dysfunction. The kinin receptors could therefore constitute potential therapeutic targets in the treatment of myocardial ischemia and Diabetic Cardiomyopathy.
-
gene deletion of the kinin receptor b1 attenuates cardiac inflammation and fibrosis during the development of experimental Diabetic Cardiomyopathy
Diabetes, 2009Co-Authors: Dirk Westermann, Heinzpeter Schultheiss, Konstantinos Savvatis, Thomas Walther, Felcicitas Escher, Meike Sobirey, Alexander Riad, Michael Bader, Carsten TschopeAbstract:OBJECTIVE Diabetic Cardiomyopathy is associated with increased mortality in patients with diabetes. The underlying pathology of this disease is still under discussion. We studied the role of the kinin B1 receptor on the development of experimental Diabetic Cardiomyopathy. RESEARCH DESIGN AND METHODS We utilized B1 receptor knockout mice and investigated cardiac inflammation, fibrosis, and oxidative stress after induction of streptozotocin (STZ)-induced diabetes. Furthermore, the left ventricular function was measured by pressure-volume loops after 8 weeks of diabetes. RESULTS B1 receptor knockout mice showed an attenuation of Diabetic Cardiomyopathy with improved systolic and diastolic function in comparison with Diabetic control mice. This was associated with a decreased activation state of the mitogen-activated protein kinase p38, less oxidative stress, as well as normalized cardiac inflammation, shown by fewer invading cells and no increase in matrix metalloproteinase-9 as well as the chemokine CXCL-5. Furthermore, the profibrotic connective tissue growth factor was normalized, leading to a reduction in cardiac fibrosis despite severe hyperglycemia in mice lacking the B1 receptor. CONCLUSIONS These findings suggest that the B1 receptor is detrimental in Diabetic Cardiomyopathy in that it mediates inflammatory and fibrotic processes. These insights might have useful implications on future studies utilizing B1 receptor antagonists for treatment of human Diabetic Cardiomyopathy.
-
myocardial overexpression of adenine nucleotide translocase 1 ameliorates Diabetic Cardiomyopathy in mice
Experimental Physiology, 2009Co-Authors: Heinzpeter Schultheiss, Yong Wang, Linda Ebermann, Anja Sternerkock, Sylwia Wika, Andrea Dorner, Thomas WaltherAbstract:Mitochondrial dysfunction is implicated in the pathogenesis of Diabetic Cardiomyopathy, a common complication of diabetes. Adenosine nucleotide translocase (ANT) translocates ADP/ATP across the inner mitochondrial membrane. Our study aimed to test the hypothesis that overexpression of ANT1 in cardiomyocytes has cardioprotective effects in Diabetic Cardiomyopathy induced by streptozotocin (STZ). Mice specifically overexpressing murine ANT1 in the heart were generated using α-myosin heavy chain promoter. Expression of ANT1 mRNA and protein in hearts was characterized by real-time polymerase chain reaction and Western blot analysis. Five- to 6-month-old male transgenic mice and their age-matched wild-type littermates were subjected to type 1 diabetes induced by STZ. Six weeks later, haemodynamic measurement was performed to assess cardiac function. Ventricular mRNA expression of atrial natriuretic peptide, a molecular marker of heart failure, was characterized by RNase-protection assay. Both ANT1 mRNA and ANT1 protein were specifically overexpressed in the heart of transgenic mice. Heart weight was decreased and cardiac function was dramatically impaired in wild-type mice 6 weeks after induction of diabetes, but ANT1 overexpression prevented these significant changes. The mRNA expression level of atrial natriuretic peptide confirmed the haemodynamic findings, being upregulated in wild-type mice receiving STZ, but showing no statistical differences in ANT1 transgenic mice. Cardiomyocyte-restricted overexpression of ANT1 prevents the development of Diabetic Cardiomyopathy; therefore, accelerated ADP/ATP exchange could be a new promising target to treat Diabetic Cardiomyopathy.
-
transgenic activation of the kallikrein kinin system inhibits intramyocardial inflammation endothelial dysfunction and oxidative stress in experimental Diabetic Cardiomyopathy
The FASEB Journal, 2005Co-Authors: Carsten Tschope, Heinzpeter Schultheiss, Thomas Walther, Michael Bader, Felicitas Escher, Frank Spillmann, Christine Altmann, Ingolf Schimke, Carlos F Sanchezferrer, Michel NoutsiasAbstract:The mechanisms contributing to Diabetic Cardiomyopathy, as well as the protective pathways of the kallikrein-kinin-system (KKS), are incompletely understood. In a kallikrein-overexpressing rat model of streptozotocin (STZ)-induced Diabetic Cardiomyopathy, we investigated the involvement of inflammatory pathways, endothelial dysfunction, and oxidative stress. Six weeks after STZ injection, impairment of left ventricular (LV) function parameters measured by a Millar-tip catheter (peak LV systolic pressure; dP/dtmax; dP/dtmin) was accompanied by a significant increment of ICAM-1 and VCAM-1 (CAMs) expression, as well as of beta2-leukocyte-integrins+ (CD18+, CD11a+, CD11b+) and cytokine (TNF-alpha and IL-1beta)-expressing infiltrates in male Sprague-Dawley (SD-STZ) rats compared with normoglycemic littermates. Furthermore, SD-STZ rats demonstrated a significant impairment of endothelium-dependent relaxation evoked by acetylcholine and significantly increased plasma TBARS (plasma thiobarbituric acid reactive substances) levels as a measure of oxidative stress. These Diabetic Cardiomyopathy-associated alterations were significantly attenuated (P<0.05) in Diabetic transgenic rats expressing the human kallikrein 1 (hKLK1) gene with STZ-induced diabetes. CAMs expression, beta2-leukocyte-integrins+, and cytokine-expressing infiltrates correlated significantly with all evaluated LV function parameters. The multiple protective effects of the KKS in experimental Diabetic Cardiomyopathy comprise the inhibition of intramyocardial inflammation (CAMs expression, beta2-leukocyte-integrins+ infiltration and cytokine expression), an improvement of endothelium-dependent relaxation and the attenuation of oxidative stress. These insights might have therapeutic implications also for human Diabetic Cardiomyopathy.
-
transgenic activation of the kallikrein kinin system inhibits intramyocardial inflammation endothelial dysfunction and oxidative stress in experimental Diabetic Cardiomyopathy
The FASEB Journal, 2005Co-Authors: Carsten Tschope, Thomas Walther, Michael Bader, Felicitas Escher, Frank Spillmann, Christine Altmann, Ingolf Schimke, Carlos F Sanchezferrer, Jing Du, Heinzpeter SchultheissAbstract:SPECIFIC AIMSIn light of the possible involvement of intramyocardial inflammation in Diabetic Cardiomyopathy, we investigated cardiac CAMs expression (ICAM-1 and VCAM-1) and β2-leukocyte integrins+...
Thomas Walther - One of the best experts on this subject based on the ideXlab platform.
-
gene deletion of the kinin receptor b1 attenuates cardiac inflammation and fibrosis during the development of experimental Diabetic Cardiomyopathy
Diabetes, 2009Co-Authors: Dirk Westermann, Heinzpeter Schultheiss, Konstantinos Savvatis, Thomas Walther, Felcicitas Escher, Meike Sobirey, Alexander Riad, Michael Bader, Carsten TschopeAbstract:OBJECTIVE Diabetic Cardiomyopathy is associated with increased mortality in patients with diabetes. The underlying pathology of this disease is still under discussion. We studied the role of the kinin B1 receptor on the development of experimental Diabetic Cardiomyopathy. RESEARCH DESIGN AND METHODS We utilized B1 receptor knockout mice and investigated cardiac inflammation, fibrosis, and oxidative stress after induction of streptozotocin (STZ)-induced diabetes. Furthermore, the left ventricular function was measured by pressure-volume loops after 8 weeks of diabetes. RESULTS B1 receptor knockout mice showed an attenuation of Diabetic Cardiomyopathy with improved systolic and diastolic function in comparison with Diabetic control mice. This was associated with a decreased activation state of the mitogen-activated protein kinase p38, less oxidative stress, as well as normalized cardiac inflammation, shown by fewer invading cells and no increase in matrix metalloproteinase-9 as well as the chemokine CXCL-5. Furthermore, the profibrotic connective tissue growth factor was normalized, leading to a reduction in cardiac fibrosis despite severe hyperglycemia in mice lacking the B1 receptor. CONCLUSIONS These findings suggest that the B1 receptor is detrimental in Diabetic Cardiomyopathy in that it mediates inflammatory and fibrotic processes. These insights might have useful implications on future studies utilizing B1 receptor antagonists for treatment of human Diabetic Cardiomyopathy.
-
myocardial overexpression of adenine nucleotide translocase 1 ameliorates Diabetic Cardiomyopathy in mice
Experimental Physiology, 2009Co-Authors: Heinzpeter Schultheiss, Yong Wang, Linda Ebermann, Anja Sternerkock, Sylwia Wika, Andrea Dorner, Thomas WaltherAbstract:Mitochondrial dysfunction is implicated in the pathogenesis of Diabetic Cardiomyopathy, a common complication of diabetes. Adenosine nucleotide translocase (ANT) translocates ADP/ATP across the inner mitochondrial membrane. Our study aimed to test the hypothesis that overexpression of ANT1 in cardiomyocytes has cardioprotective effects in Diabetic Cardiomyopathy induced by streptozotocin (STZ). Mice specifically overexpressing murine ANT1 in the heart were generated using α-myosin heavy chain promoter. Expression of ANT1 mRNA and protein in hearts was characterized by real-time polymerase chain reaction and Western blot analysis. Five- to 6-month-old male transgenic mice and their age-matched wild-type littermates were subjected to type 1 diabetes induced by STZ. Six weeks later, haemodynamic measurement was performed to assess cardiac function. Ventricular mRNA expression of atrial natriuretic peptide, a molecular marker of heart failure, was characterized by RNase-protection assay. Both ANT1 mRNA and ANT1 protein were specifically overexpressed in the heart of transgenic mice. Heart weight was decreased and cardiac function was dramatically impaired in wild-type mice 6 weeks after induction of diabetes, but ANT1 overexpression prevented these significant changes. The mRNA expression level of atrial natriuretic peptide confirmed the haemodynamic findings, being upregulated in wild-type mice receiving STZ, but showing no statistical differences in ANT1 transgenic mice. Cardiomyocyte-restricted overexpression of ANT1 prevents the development of Diabetic Cardiomyopathy; therefore, accelerated ADP/ATP exchange could be a new promising target to treat Diabetic Cardiomyopathy.
-
transgenic activation of the kallikrein kinin system inhibits intramyocardial inflammation endothelial dysfunction and oxidative stress in experimental Diabetic Cardiomyopathy
The FASEB Journal, 2005Co-Authors: Carsten Tschope, Heinzpeter Schultheiss, Thomas Walther, Michael Bader, Felicitas Escher, Frank Spillmann, Christine Altmann, Ingolf Schimke, Carlos F Sanchezferrer, Michel NoutsiasAbstract:The mechanisms contributing to Diabetic Cardiomyopathy, as well as the protective pathways of the kallikrein-kinin-system (KKS), are incompletely understood. In a kallikrein-overexpressing rat model of streptozotocin (STZ)-induced Diabetic Cardiomyopathy, we investigated the involvement of inflammatory pathways, endothelial dysfunction, and oxidative stress. Six weeks after STZ injection, impairment of left ventricular (LV) function parameters measured by a Millar-tip catheter (peak LV systolic pressure; dP/dtmax; dP/dtmin) was accompanied by a significant increment of ICAM-1 and VCAM-1 (CAMs) expression, as well as of beta2-leukocyte-integrins+ (CD18+, CD11a+, CD11b+) and cytokine (TNF-alpha and IL-1beta)-expressing infiltrates in male Sprague-Dawley (SD-STZ) rats compared with normoglycemic littermates. Furthermore, SD-STZ rats demonstrated a significant impairment of endothelium-dependent relaxation evoked by acetylcholine and significantly increased plasma TBARS (plasma thiobarbituric acid reactive substances) levels as a measure of oxidative stress. These Diabetic Cardiomyopathy-associated alterations were significantly attenuated (P<0.05) in Diabetic transgenic rats expressing the human kallikrein 1 (hKLK1) gene with STZ-induced diabetes. CAMs expression, beta2-leukocyte-integrins+, and cytokine-expressing infiltrates correlated significantly with all evaluated LV function parameters. The multiple protective effects of the KKS in experimental Diabetic Cardiomyopathy comprise the inhibition of intramyocardial inflammation (CAMs expression, beta2-leukocyte-integrins+ infiltration and cytokine expression), an improvement of endothelium-dependent relaxation and the attenuation of oxidative stress. These insights might have therapeutic implications also for human Diabetic Cardiomyopathy.
-
transgenic activation of the kallikrein kinin system inhibits intramyocardial inflammation endothelial dysfunction and oxidative stress in experimental Diabetic Cardiomyopathy
The FASEB Journal, 2005Co-Authors: Carsten Tschope, Thomas Walther, Michael Bader, Felicitas Escher, Frank Spillmann, Christine Altmann, Ingolf Schimke, Carlos F Sanchezferrer, Jing Du, Heinzpeter SchultheissAbstract:SPECIFIC AIMSIn light of the possible involvement of intramyocardial inflammation in Diabetic Cardiomyopathy, we investigated cardiac CAMs expression (ICAM-1 and VCAM-1) and β2-leukocyte integrins+...
Dov Freimark - One of the best experts on this subject based on the ideXlab platform.
-
sodium glucose cotransporter 2 inhibitor dapagliflozin attenuates Diabetic Cardiomyopathy
Cardiovascular Diabetology, 2020Co-Authors: M Arow, Maayan Waldman, Dor Yadin, Vadim Nudelman, Asher Shainberg, Nader G Abraham, Dov FreimarkAbstract:Diabetes mellitus type 2 (DM2) is a risk factor for developing heart failure but there is no specific therapy for Diabetic heart disease. Sodium glucose transporter 2 inhibitors (SGLT2I) are recently developed Diabetic drugs that primarily work on the kidney. Clinical data describing the cardiovascular benefits of SGLT2Is highlight the potential therapeutic benefit of these drugs in the prevention of cardiovascular events and heart failure. However, the underlying mechanism of protection remains unclear. We investigated the effect of Dapagliflozin—SGLT2I, on Diabetic Cardiomyopathy in a mouse model of DM2. Cardiomyopathy was induced in Diabetic mice (db/db) by subcutaneous infusion of angiotensin II (ATII) for 30 days using an osmotic pump. Dapagliflozin (1.5 mg/kg/day) was administered concomitantly in drinking water. Male homozygous, 12–14 weeks old WT or db/db mice (n = 4–8/group), were used for the experiments. Isolated cardiomyocytes were exposed to glucose (17.5–33 mM) and treated with Dapagliflozin in vitro. Intracellular calcium transients were measured using a fluorescent indicator indo-1. Angiotensin II infusion induced Cardiomyopathy in db/db mice, manifested by cardiac hypertrophy, myocardial fibrosis and inflammation (TNFα, TLR4). Dapagliflozin decreased blood glucose (874 ± 111 to 556 ± 57 mg/dl, p < 0.05). In addition it attenuated fibrosis and inflammation and increased the left ventricular fractional shortening in ATII treated db/db mice. In isolated cardiomyocytes Dapagliflozin decreased intracellular calcium transients, inflammation and ROS production. Finally, voltage-dependent L-type calcium channel (CACNA1C), the sodium–calcium exchanger (NCX) and the sodium–hydrogen exchanger 1 (NHE) membrane transporters expression was reduced following Dapagliflozin treatment. Dapagliflozin was cardioprotective in ATII-stressed Diabetic mice. It reduced oxygen radicals, as well the activity of membrane channels related to calcium transport. The cardioprotective effect manifested by decreased fibrosis, reduced inflammation and improved systolic function. The clinical implication of our results suggest a novel pharmacologic approach for the treatment of Diabetic Cardiomyopathy through modulation of ion homeostasis.