Regulation of SERCA pumps expression in diabetes

Zarain‐Herzberg, Ángel; García‐Rivas, Gerardo; Estrada-Avilés, Rafael

doi:10.1016/j.ceca.2014.09.005

Cited by 82 publications

(73 citation statements)

References 89 publications

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“…In agreement, it was reported that islets isolated from diabetic db/db mice lacked SERCA2b, the main SERCA isoform expressed in pancreatic β-cells, and revealed altered Ca 2＋ oscillations (6). In addition, a significant decrease was recorded in the mean isolated islet calcium values in the diabetic group.…”

Section: Discussionsupporting

confidence: 86%

“…On the day following confirmation of diabetes, 1×10 6 of cultured and labeled rat AMSCs, suspended in 1 ml PBS, were injected into the tail vein (10).…”

Section: Donor Groupmentioning

confidence: 99%

“…In the diabetic pancreas, the amount of SERCA2b is decreased in the β-cells leading to impaired intracellular Ca 2＋ homeostasis and insulin secretion. Increasing the level of SERCA2b in pancreas by gene therapy is a promising therapeutic strategy to correct alterations in Ca 2＋ handling in diabetic patients (6).…”

Section: Introductionmentioning

confidence: 99%

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Effect of Stem Cells and Gene Transfected Stem Cells Therapy on the Pancreas of Experimentally Induced Type 1 Diabetes

Zickri

Aboul-Fotouh

Omar

et al. 2018

IJSC

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Background and Objectives: Insulin secretion entirely depends on Ca 2＋ influx and sequestration into endoplasmic reticulum (ER) of β-cells, performed by Sarco-ER Ca 2＋-ATPase 2b (SERCA2b). In diabetes, SERCA2b is decreased in the β-cells leading to impaired intracellular Ca 2＋ homeostasis and insulin secretion. Adipose mesenchymal stem cells (AMSCs) play a potential role in transplantation in animal models. The present study aimed at investigating and comparing the therapeutic effect of non-transfected AMSCs and SERCA2b gene transfected AMSCs on the pancreas of induced diabetes type 1 in rat. Methods and Results: 58 adult male albino rats were divided into: Donor group: 22 rats, 2 for isolation, propagation and characterization of AMSCs and SERCA2b transfected AMSCs, in addition 20 for isolated islet calcium level assessment. Group І (Control Group): 6 rats, Group II (Diabetic Group): 10 rats, 50 mg streptozotocin (STZ) were injected intraperitoneal (IP), Group III (AMSCs Group): 10 rats, 1×10 6 AMSCs were injected intravenous and Group IV (SERCA2b transfected AMSCs Group): 10 rats, 1×10 6 SERCA2b transfected AMSCs were injected as in group III. Groups I, II, III and IV were sacrified 3 weeks following confirmation of diabetes. Serological, histological, morphometric studies and quantitative polymerase chain reaction (qPCR) were performed. Nuclear, cytoplasmic degenerative and extensive fibrotic changes were detected in the islets of group II that regressed in groups III and IV. Isolated islet calcium, blood glucose, plasma insulin and qPCR were confirmative. Conclusions: AMSCs and SERCA2b gene transfected AMSCs therapy proved definite therapeutic effect, more obvious in response to SERCA2b gene transfected AMSCs.

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Section: Discussionsupporting

confidence: 86%

“…On the day following confirmation of diabetes, 1×10 6 of cultured and labeled rat AMSCs, suspended in 1 ml PBS, were injected into the tail vein (10).…”

Section: Donor Groupmentioning

confidence: 99%

See 1 more Smart Citation

Effect of Stem Cells and Gene Transfected Stem Cells Therapy on the Pancreas of Experimentally Induced Type 1 Diabetes

Zickri

Aboul-Fotouh

Omar

et al. 2018

IJSC

View full text Add to dashboard Cite

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“…However, plasma nitrite/nitrate levels (reflecting NO bioavailability) were not diminished. In addition, SERCA2a gene expression was significantly lower, which might reflect the disturbance of intracellular Ca 2+ homeostasis and could contribute to the prolonged relaxation time in T2DM 27. Vardenafil, however, significantly affected the DM‐associated nitro‐oxidative stress as it prevented an increase of 3‐NT staining and the elevation of catalase and thioredoxin‐1 in the ZDF group myocardium.…”

Section: Discussionmentioning

confidence: 97%

Prevention of the development of heart failure with preserved ejection fraction by the phosphodiesterase‐5A inhibitor vardenafil in rats with type 2 diabetes

Mátyás

Németh

Oláh

et al. 2016

European J of Heart Fail

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AimsHeart failure with preserved ejection fraction (HFpEF) has a great epidemiological burden. The pathophysiological role of cyclic guanosine monophosphate (cGMP) signalling has been intensively investigated in HFpEF. Elevated levels of cGMP have been shown to exert cardioprotective effects in various cardiovascular diseases, including diabetic cardiomyopathy. We investigated the effect of long‐term preventive application of the phosphodiesterase‐5A (PDE5A) inhibitor vardenafil in diabetic cardiomyopathy‐associated HFpEF.Methods and resultsZucker diabetic fatty (ZDF) rats were used as a model of HFpEF and ZDF lean rats served as controls. Animals received vehicle or 10 mg/kg body weight vardenafil per os from weeks 7 to 32 of age. Cardiac function, morphology was assessed by left ventricular (LV) pressure–volume analysis and echocardiography at week 32. Cardiomyocyte force measurements were performed. The key markers of cGMP signalling, nitro‐oxidative stress, apoptosis, myocardial hypertrophy and fibrosis were examined. The ZDF animals showed diastolic dysfunction (increased LV/cardiomyocyte stiffness, prolonged LV relaxation time), preserved systolic performance, decreased myocardial cGMP level coupled with impaired protein kinase G (PKG) activity, increased nitro‐oxidative stress, enhanced cardiomyocyte apoptosis, and hypertrophic and fibrotic remodelling of the myocardium. Vardenafil effectively prevented the development of HFpEF by maintaining diastolic function (decreased LV/cardiomyocyte stiffness and LV relaxation time), by restoring cGMP levels and PKG activation, by lowering apoptosis and by alleviating nitro‐oxidative stress, myocardial hypertrophy and fibrotic remodelling.ConclusionsWe report that vardenafil successfully prevented the development of diabetes mellitus‐associated HFpEF. Thus, PDE5A inhibition as a preventive approach might be a promising option in the management of HFpEF patients with diabetes mellitus.

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“…In a rabbit model of congestive heart failure, pacing improves contractility concomitant with upregulation of SERCA-2a and miR-133a (37). In heart failure and diabetic cardiomyopathy, SERCA-2a is downregulated (38). Our results demonstrate that miR-133a mimic treatment upregulates SERCA-2a in diabetic hearts (Fig.…”

Section: Discussionmentioning

confidence: 99%

Lack of miR-133a Decreases Contractility of Diabetic Hearts: A Role for Novel Cross Talk Between Tyrosine Aminotransferase and Tyrosine Hydroxylase

et al. 2016

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MicroRNAs (miRNAs) have a fundamental role in diabetic heart failure. The cardioprotective miRNA-133a (miR-133a) is downregulated, and contractility is decreased in diabetic hearts. Norepinephrine (NE) is a key catecholamine that stimulates contractility by activating β-adrenergic receptors (β-AR). NE is synthesized from tyrosine by the rate-limiting enzyme, tyrosine hydroxylase (TH), and tyrosine is catabolized by tyrosine aminotransferase (TAT). However, the cross talk/link between TAT and TH in the heart is unclear. To determine whether miR-133a plays a role in the cross talk between TH and TAT and regulates contractility by influencing NE biosynthesis and/or β-AR levels in diabetic hearts, Sprague-Dawley rats and miR-133a transgenic (miR-133aTg) mice were injected with streptozotocin to induce diabetes. The diabetic rats were then treated with miR-133a mimic or scrambled miRNA. Our results revealed that miR-133a mimic treatment improved the contractility of the diabetic rat’s heart concomitant with upregulation of TH, cardiac NE, β-AR, and downregulation of TAT and plasma levels of NE. In miR-133aTg mice, cardiac-specific miR-133a overexpression prevented upregulation of TAT and suppression of TH in the heart after streptozotocin was administered. Moreover, miR-133a overexpression in CATH.a neuronal cells suppressed TAT with concomitant upregulation of TH, whereas knockdown and overexpression of TAT demonstrated that TAT inhibited TH. Luciferase reporter assay confirmed that miR-133a targets TAT. In conclusion, miR-133a controls the contractility of diabetic hearts by targeting TAT, regulating NE biosynthesis, and consequently, β-AR and cardiac function.

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Regulation of SERCA pumps expression in diabetes

Cited by 82 publications

References 89 publications

Effect of Stem Cells and Gene Transfected Stem Cells Therapy on the Pancreas of Experimentally Induced Type 1 Diabetes

Effect of Stem Cells and Gene Transfected Stem Cells Therapy on the Pancreas of Experimentally Induced Type 1 Diabetes

Prevention of the development of heart failure with preserved ejection fraction by the phosphodiesterase‐5A inhibitor vardenafil in rats with type 2 diabetes

Lack of miR-133a Decreases Contractility of Diabetic Hearts: A Role for Novel Cross Talk Between Tyrosine Aminotransferase and Tyrosine Hydroxylase

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