Metabolic disturbances in diabetic cardiomyopathy

Rodrigues, Brian; Cam, Margaret C.; McNeill, John H.

doi:10.1007/978-1-4615-5687-9_5

Cited by 106 publications

(130 citation statements)

References 36 publications

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“…Several factors have been reported to be involved in the pathogenesis of this disease, including hyperglycemia, insulin resistance and oxidative stress-induced insults (3,4,5). Among these factors, hyperglycemia is considered one of the most important factors in the onset of diabetic cardiomyopathy (4,6).…”

Section: Introductionmentioning

confidence: 99%

Exogenous hydrogen sulfide protects H9c2 cardiac cells against high glucose-induced injury by inhibiting the activities of the p38 MAPK and ERK1/2 pathways

Wang

Chen

et al. 2013

International Journal of Molecular Medicine

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Abstract. Hyperglycemia is a risk factor for the development of diabetic cardiovascular complications, which are associated with the activation of the mitogen-activated protein kinase (MAPK) signaling pathway. In this study, we demonstrate the inhibitory effects of exogenous hydrogen sulfide (H 2 S) on the activation of the MAPK pathway. The aim of the present study was to determine whether exogenous H 2 S prevents high glucose (HG)-induced injury by inhibiting the activation of the p38 MAPK and extracellular signal-regulated kinase (ERK)1/2 (members of MAPK) pathways in cardiomyoblasts (H9c2 cells). The findings of the present study demonstrated that the treatment of H9c2 cells with HG (35 mM glucose) for 24 h not only significantly induced injury, including cytotoxicity, apoptosis, overproduction of reactive oxygen species (ROS) and the loss of mitochondrial membrane potential (MMP), but also upregulated the expression levels of phosphorylated (p)-p38 MAPK and p-ERK1/2. The increased expression levels of p-p38 MAPK and p-ERK1/2 were markedly reduced by pre-treatment of the H9c2 cells with 400 µM sodium hydrogen sulfide (NaHS; a donor of H 2 S) prior to exposure to 35 mM glucose. Importantly, pre-treatment of the cells with 400 µM NaHS or 3 µM SB203580 (a selective inhibitor of p38 MAPK) or 15 µM U0126 (a selective inhibitor of ERK1/2) attenuated the HG-induced cardiomyocyte injury, leading to an increase in cell viability and a decrease in the number of apoptotic cells, preventing ROS generation, as well as the loss of MMP. In addition, pre-treatment of the cells with 1,000 µM N-acetyl-L-cysteine (a ROS scavenger) prior to exposure to HG ameliorated the HG-induced cytotoxicity. Taken together, the data from the present study demonstrate for the first time, to our knowledge, that exogenous H 2 S exerts a protective effect against HG-induced injury by inhibiting the activation of the p38 MAPK and ERK1/2 pathways and preventing oxidative stress in H9c2 cells.

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Section: Introductionmentioning

confidence: 99%

Exogenous hydrogen sulfide protects H9c2 cardiac cells against high glucose-induced injury by inhibiting the activities of the p38 MAPK and ERK1/2 pathways

Wang

Chen

et al. 2013

International Journal of Molecular Medicine

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“…The most prominent defects of diabetic cardiomyopathy include compromised ventricular functions such as prolonged duration of contraction and relaxation and reduced cardiac compliance (Fein 1990, Ren & Davidoff 1997, Ren & Bode 2000. The etiology of diabetic cardiomyopathy is rather complex and may involve metabolic derangements, depressed autonomic function and abnormalities in certain hormones or proteins that regulate intracellular ion homeostasis, particularly Ca 2+ (Fein 1990, Rodrigues et al 1998, Norby et al 2002. Nevertheless, either endogenous overexpression or exogenous administration of a key cardiac surviving factor, insulin-like growth factor I (IGF-I) has exhibited beneficial effects on diabetes-induced cardiac mechanical dysfunction and oxidative damage (Kajstura et al 2001, Norby et al 2002.…”

Section: Introductionmentioning

confidence: 99%

Transgenic overexpression of insulin-like growth factor I prevents streptozotocin-induced cardiac contractile dysfunction and beta-adrenergic response in ventricular myocytes

Norby¹,

Ns²,

Kajstura³

et al. 2004

Journal of Endocrinology

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Diabetic cardiomyopathy is characterized by cardiac dysfunction and altered level/function of insulin-like growth factor I (IGF-I). Both endogenous and exogenous IGF-I have been shown to effectively alleviate diabetes-induced cardiac dysfunction and oxidative stress. This study was designed to examine the effect of cardiac overexpression of IGF-I on streptozotocin (STZ)-induced cardiac contractile dysfunction in mouse myocytes. Both IGF-I heterozygous transgenic mice and their wild-type FVB littermates were made diabetic with a single injection of STZ (200 mg/kg, i.p.) and maintained for 2 weeks. The following mechanical indices were evaluated in ventricular myocytes: peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR 90 ) and maximal velocity of shortening/ relengthening ( dL/dt , were prevented by the IGF-I transgene. In addition, myocytes from STZ-treated FVB mice displayed an attenuated contractile response to the -adrenergic agonist isoproterenol, which was restored by the IGF-I transgene. Contractile response to the -adrenergic agonist phenylephrine and angiotensin II was not affected by either STZ treatment or IGF-I. These results validate the beneficial role of IGF-I in diabetic cardiomyopathy, possibly due to an improved -adrenergic response.

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“…4 -6 Several factors have been postulated to contribute to the pathogenesis of diabetic cardiomyopathy, including hyperglycemia, insulin resistance, and free-radical damage, 3,4 among which hyperglycemia is considered one of the most important factors in the onset of diabetic cardiomyopathy. 4,7 The renin-angiotensin system (RAS) plays a major role in the regulation of blood pressure and other cardiovascular functions. Enhanced RAS activity has been demonstrated in several cardiovascular diseases, such as diabetes and hypertension, and might play a role in the pathogenesis of congestive heart failure, coronary insufficiency, and hypertensive cardiomyopathy.…”

mentioning

confidence: 99%

AT ₁ Blockade Prevents Glucose-Induced Cardiac Dysfunction in Ventricular Myocytes

et al. 2003

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Abstract-Enhanced tissue angiotensin (Ang) II levels have been reported in diabetes and might lead to cardiac dysfunction through oxidative stress. This study examined the effect of blocking the Ang II type 1 (AT 1 ) receptor on high glucose-induced cardiac contractile dysfunction. Rat ventricular myocytes were maintained in normal-(NG, 5.5 mmol/L) or high-(HG, 25.5 mmol/L) glucose medium for 24 hours. Mechanical and intracellular Ca 2ϩ properties were assessed as peak shortening (PS), time to PS (TPS), time to 90% relengthening (TR 90 ), maximal velocity of shortening/relengthening (ϮdL/dt), and intracellular Ca 2ϩ decay (). HG myocytes exhibited normal PS; decreased ϮdL/dt; and prolonged TPS, TR 90 , and . Interestingly, the HG-induced abnormalities were prevented with the AT 1 blocker L-158,809 (10 to 1000 nmol/L) but not the Janus kinase-2 (JAK2) inhibitor AG-490 (10 to 100 mol/L). The only effect of AT 1 blockade on NG myocytes was enhanced PS at 1000 nmol/L. AT 1 antagonist-elicited cardiac protection against HG was nullified by the NADPH oxidase activator sodium dodecyl sulfate (80 mol/L) and mimicked by the NADPH oxidase inhibitors diphenyleneiodonium (10 mol/L) or apocynin (100 mol/L). Western blot analysis confirmed that the protein abundance of NADPH oxidase subunit p47 phox and the AT 1 but not the AT 2 receptor was enhanced in HG myocytes. In addition, the HG-induced increase of p47 phox was prevented by L-158,809. Enhanced reactive oxygen species production observed in HG myocytes was prevented by AT 1 blockade or NADPH oxidase inhibition. Collectively, our data suggest that local Ang II, acting via AT 1 receptor-mediated NADPH oxidase activation, is involved in hyperglycemia-induced cardiomyocyte dysfunction, which might play a role in diabetic cardiomyopathy.

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Metabolic disturbances in diabetic cardiomyopathy

Cited by 106 publications

References 36 publications

Exogenous hydrogen sulfide protects H9c2 cardiac cells against high glucose-induced injury by inhibiting the activities of the p38 MAPK and ERK1/2 pathways

Exogenous hydrogen sulfide protects H9c2 cardiac cells against high glucose-induced injury by inhibiting the activities of the p38 MAPK and ERK1/2 pathways

Transgenic overexpression of insulin-like growth factor I prevents streptozotocin-induced cardiac contractile dysfunction and beta-adrenergic response in ventricular myocytes

AT ₁ Blockade Prevents Glucose-Induced Cardiac Dysfunction in Ventricular Myocytes

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Metabolic disturbances in diabetic cardiomyopathy

Cited by 106 publications

References 36 publications

Exogenous hydrogen sulfide protects H9c2 cardiac cells against high glucose-induced injury by inhibiting the activities of the p38 MAPK and ERK1/2 pathways

Exogenous hydrogen sulfide protects H9c2 cardiac cells against high glucose-induced injury by inhibiting the activities of the p38 MAPK and ERK1/2 pathways

Transgenic overexpression of insulin-like growth factor I prevents streptozotocin-induced cardiac contractile dysfunction and beta-adrenergic response in ventricular myocytes

AT 1 Blockade Prevents Glucose-Induced Cardiac Dysfunction in Ventricular Myocytes

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AT ₁ Blockade Prevents Glucose-Induced Cardiac Dysfunction in Ventricular Myocytes